Aromatic amides, method for preparing and compositions containing same, and use thereof as pesticides

ABSTRACT

The subject of the invention is the compounds of formula (I): 
     
         Q(CH.sub.2)a-(X.sub.1).sub.b -Q.sub.1 -Q.sub.2 
    
      -C(X 2 )--N(R 1 )(R 2 )                          (I) 
     in which: 
     Q represents an aryl radical, 
     X 1  represents oxy, thio, sulphinyl or sulphonyl, 
     X 2  represents oxygen or sulphur, 
     Q 1  represents a cyclopropanediyl radical, 
     Q 2  represents an arylene radical, 
     R 1  and R 2  represent: 
     either a hydrogen atom or a hydrocarbon radical or one of the groups 
     
         R.sub.3 --C═X.sub.3, (R.sub.3).sub.2 --P═X.sub.3, T.sub.2 -R.sub.5 
    
      or S(O) j  --N(R 6 )(R 7 ) 
     in which X 3  represents an oxygen atom or a sulphur atom, T 2  represents a bivalent oxy, carbonyl or oxycarbonyl group and j is equal to 0, 1 or 2, their preparation process and their use as pesticides.

The present invention relates to new aromatic amides, their preparation process, the compositions containing them and their use as pesticides.

Certain 5-cyclopropyl pentadieneamides are described in the European Patent Applications published under the numbers 0,369,762, 0,524,041 and 0,553,081 as having such properties.

It has now been found that the compounds corresponding to formula (I) as defined hereafter also have useful pesticide properties, which make them capable of being used for the protection of plants, safeguarding hygiene in public or private premises, as well as for the implementation of therapeutic treatment for veterinary use, or even for human use.

The products of formula (I) are moreover photostable and not very toxic for mammals and therefore correspond perfectly to the requirements of the modern agrochemical industry.

Therefore a subject of the present invention is in all their stereoisomeric forms or in the form of stereoisomer mixtures, the compounds of formula (I):

    Q(CH.sub.2).sub.a -(X.sub.1).sub.b -Q.sub.1 -Q.sub.2 -C(X.sub.2)--N(R.sub.1)(R.sub.2)                          (I)

in which:

Q represents an aryl radical or a radical derived from a condensed bicyclic hydrocarbon containing a benzene ring, which is linked to an adjacent (CH₂)_(a) group by a carbon atom of said benzene ring, Q contains 6 to 12 carbon atoms and can be either non-substituted or substituted, a and b are identical or different and independently of each other are equal to 0 or to 1,

X₁ represents a bivalent oxy, thio, sulphinyl or sulphonyl radical,

X₂ represents an oxygen atom or a sulphur atom,

Q₁ represents a cyclopropanediyl radical, which is either non-substituted or substituted,

Q₂ represents an arylene radical or a radical derived from a condensed bicyclic hydrocarbon containing a benzene ring, which is linked to the adjacent Q₁ and C(X₂) groups by two carbon atoms of said benzene ring, Q₂ contains 6 to 12 carbon atoms and can independently of Q, be either non-substituted or substituted,

R₁ and R₂ represent independently of each other: either a hydrogen atom,

or a radical derived from a saturated or unsaturated, linear or branched, aromatic or non-aromatic, cyclic or acyclic hydrocarbon, and containing 1 to 12 carbon atoms, itself being able to be either non-substituted or substituted, or a radical derived from a linear or branched structure containing 1 to 20 carbon atoms and 1 to 6 heteroatoms chosen from oxygen, nitrogen or sulphur atoms, itself being able to be either non-substituted or substituted, or a radical derived from an aromatic or non-aromatic heterocycle containing 5 to 9 carbon atoms and 1 to 4 heteroatoms chosen from oxygen, nitrogen or sulphur atoms, this radical being able to be non-substituted or substituted, or a group (A): ##STR1## in which X₃ represents an oxygen atom or a sulphur atom, and R₃ represents a hydrogen atom or an R₄ -(T₁)_(i) group in which i is equal to 0 or to 1, T₁ represents a bivalent oxy, carbonyl or oxycarbonyl group and R₄ represents a hydrogen atom or a radical derived from a saturated or unsaturated, linear or branched, aromatic or non-aromatic, cyclic or acyclic hydrocarbon, and containing 1 to 20 carbon atoms, itself being able to be either non-substituted or substituted, or a group (B): ##STR2## in which R₃ and X₃ are as defined above, or a group (C):

    --T.sub.2 --R.sub.5

in which T2 represents a bivalent thia, sulphinyl, sulphonyl or sulphonyloxy radical and R₅ represents an hydrogen atom or a radical derived from a saturated or unsaturated, linear or branched, aromatic or non-aromatic, cyclic or acyclic hydrocarbon, and containing 1 to 8 carbon atoms, itself being able to be either non-substituted or substituted, or a group (D):

    [S(O).sub.j ].sub.k --N(R.sub.6)(R.sub.7)

in which j is equal to 0, 1 or 2, k is equal to 0 or 1, R₆ represents a hydrogen atom or a radical derived from a saturated or unsaturated, linear or branched, aromatic or non-aromatic, cyclic or acyclic hydrocarbon, and containing 1 to 8 carbon atoms, itself being able to be either non-substituted or substituted, and R₇ represents a carboxy, fluorocarbonyl, alkoxycarbonyl group containing 2 to 5 carbon atoms, or an acyl radical containing 1 to 5 carbon atoms, or an alkyl radical containing 1 to 4 carbon atoms substituted by a cyano group or by an alkoxycarbonyl radical containing 2 to 5 carbon atoms, or an acyl radical containing 1 to 5 carbon atoms, or by an aryl radical containing 6 to 10 carbon atoms, non-substituted or substituted by one or more groups chosen from halo, cyano, nitro, trifluoromethyl, trifluoro-methoxy, trifluoromethylthio groups or alkyl radicals containing 1 to 4 carbon atoms or alkoxy radicals containing 1 to 4 carbon atoms or R₆ and R₇ form together with the nitrogen atom to which they are linked a nitrogenous heterocycle containing 3 to 10 members containing optionally one or more cyclic heteroatoms chosen among oxygen, nitrogen or sulphur and optionally substituted,

or R₁ and R₂ represent together with the nitrogen atom to which they are linked a nitrogenous heterocycle containing 3 to 10 members containing optionally one or more cyclic heteroatoms chosen among oxygen, nitrogen or sulphur and optionally substituted, it being understood that in said formula (I) when Q represents a 2-(phenylamino-carbonyl) phenyl radical, Q₁ a 1,2-cyclopropanediyl radical, Q₂ an ortho-phenylene radical, X₂ an oxygen atom, R₂ a hydrogen atom and a and b are equal to 0, R₁ does not represent a phenyl radical.

By compound of formula (I) is designated all the possible geometric isomers and stereoisomers taken individually or in a mixture.

By radical derived from a condensed bicyclic hydrocarbon containing a benzene ring, is designated in particular for the definition of Q the indanyl, indenyl, dihydronaphthyl or tetrahydronaphthyl radicals and for the definition of Q₂ in particular the following radicals: ortho-phenylene, meta-phenylene, para-phenylene, 1,2-naphthylene, 1,3-naphthylene, 1,4-naphthylene, 4,5-indenylene, 4,6-indenylene, 4,7-indenylene, 4,5-indanylene, 4,6-indanylene, 4,7-indanylene, 1,2,3,4-tetrahydro 5,6-naphthylene, 1,2,3,4-tetrahydro 5,7-naphthylene, 5,8-tetrahydronaphthylene.

By radical derived from a saturated or unsaturated, aromatic or non-aromatic, cyclic hydrocarbon, is designated in particular the phenyl radical, cycloalkyl radicals such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl radicals as well as alkyl radicals substituted by a cyclic radical such as the benzyl or cyclopropylmethyl radical.

By radical derived from a saturated or unsaturated, linear or branched, acyclic hydrocarbon, is designated alkyl radicals such as in particular methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl or isohexyl, alkenyl radicals, such as in particular vinyl, 1-propenyl, 2-methyl 2-propenyl, isopropenyl radicals, alkynyl radicals such as in particular ethynyl, 1-propynyl, 2-propynyl radicals as well as radicals containing several unsaturations such as alkadienyl radicals such as 1,3-butadienyl or pent-2-ene-4-ynyl radical.

By radical derived from a linear or branched structure, containing 1 to 20 carbon atoms and 1 to 6 heteroatoms, is designated in particular the radicals derived from alkanes some of the carbon atoms of which are replaced by oxygen, sulphur atoms or an --NH-- group, such as the following radicals: hydroxymethyl, methoxymethyl, ethoxymethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-(2-methoxy ethoxy) ethyl, (2-methoxyethoxy) methyl, [2-(2-methoxy ethoxy) ethoxy] methyl, ethoxymethyl, [2-(2-butoxy ethoxy) ethoxy] methyl, 2-methylthio ethyl, 2-(methylamino) ethyl, methylaminomethyl, butylaminobutyl or propoxymethyl.

By radical derived from an aromatic or non-aromatic heterocycle, is designated in particular the following radicals: thienyl, furyl, pyrannyl, pyrrolyl, 2H-pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, isothiazolyl, isoxazolyl, furazannyl, thiazolyl, oxazolyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, pyrazolinyl, piperidyl, piperazinyl, morpholinyl, azepinyl, thiazinyl, tetrazinyl, oxathiolannyl or thiadiazinyl.

When Q is substituted by one or more substituants, these substituents are chosen in particular from halogen atoms or the following groups: methylenedioxy, difluoromethylenedioxy, tetrafluoro ethylenedioxy, cyano, nitro, cyanato, thiocyanato, pentafluorothio, fluorosulphonyl or R-(T)_(c) - in which R represents a hydrogen atom or a radical derived from a saturated or unsaturated, linear or branched, aromatic or non-aromatic, cyclic or acyclic hydrocarbon and containing 1 to 8 carbon atoms, itself being able to be either non-substituted or substituted by one or more halogen atoms, c is equal to 0 or 1 and T represents a bivalent oxy, carbonyl, carbonyloxy, oxycarbonyl, thio, sulphinyl, sulphonyl, or sulphonyloxy group, a --(CO)_(d) --N(R')--(CO)_(e) --(O)_(f) -- or --N(R")--S(O)_(g) -- group in which R' and R" represent independently of R a hydrogen atom, or a radical derived from a saturated or unsaturated, linear or branched, aromatic or non-aromatic, cyclic or acyclic hydrocarbon and containing 1 to 8 carbon atoms, itself being able to be either non-substituted or substituted by one or more halogen atoms, d, e and f are equal to 0 or 1, f is equal to 0 when e is equal to 0, the sum of e+d is equal to 0 or 1, and g is equal 0, 1 or 2.

When Q₁ is substituted, the substituents are chosen in particular from halogen atoms, cyano, azido radicals, or saturated or unsaturated, aliphatic radicals containing 1 to 4 carbon atoms non-substituted or substituted by one or more halogen atoms, such as methyl, vinyl or ethynyl radicals.

When Q₂ is substituted, these substituents are chosen in particular from halogen atoms or methylenedioxy, difluoro-methylenedioxy, tetrafluoro ethylenedioxy, cyano, nitro, amino, alkylamino, alkenylamino, cyanato, thiocyanato, penta-fluorothio, fluorosulphonyl groups or an R-(T)_(c) - group in which R represents a hydrogen atom or a radical derived from a saturated or unsaturated, linear or branched, aromatic or non-aromatic, cyclic or acyclic hydrocarbon and containing 1 to 8 carbon atoms, itself being able to be either non-substituted or substituted by one or more halogen atoms, c is equal to 0 or 1 and T represents a bivalent oxy, carbonyl, carbonyloxy, oxycarbonyl, thio, sulphinyl, sulphonyl, or sulphonyloxy group, a --(CO)_(d) --N(R')--(CO)_(e) --(O)_(f) -- or --N(R")--S(O)_(g) -- group in which R', R", d, e, f and g are as defined previously.

When in what precedes or in what follows, it is indicated that a radical can be substituted by one or more halogen atoms, these halogen atoms can be fluorine, chlorine, bromine or iodine atoms. When it is a radical poly-substituted by fluorine atoms, the perfluorinated radicals are in particular designated.

When in what precedes, a radical derived from a saturated or unsaturated, linear or branched, aromatic or non-aromatic, cyclic or acyclic hydrocarbon is substituted, these substituents are chosen in particular from halogen atoms or the methylenedioxy, difluoromethylenedioxy, tetrafluoro ethylenedioxy, cyano, nitro, cyanato, thiocyanato, pentafluorothio, fluorosulphonyl groups or an R-(T)_(c) - group in which R represents a hydrogen atom or a radical derived from a saturated or unsaturated, linear or branched, aromatic or non-aromatic, cyclic or acyclic hydrocarbon and containing 1 to 8 carbon atoms and optionally one or more heteroatoms, itself being able to be either non substituted or substituted by one or more halogen atoms, c is equal 0 or to 1 and T represents a bivalent oxy, carbonyl, carbonyloxy, oxycarbonyl, thio, sulphinyl, sulphonyl, or sulphonyloxy group, a --(CO)_(d) --N(R')--(CO)_(e) --(O)_(f) -- or --N(R")--S(O)_(g) -- group in which R', R", d, e, f and g are as defined previously.

The compounds of formula (I) in which Q, Q₁, Q₂ are non-substituted or substituted as described in the preceding paragraphs, constitute a first preferred variant of the present invention.

In a second preferred variant of the present invention, Q represents a phenyl radical or a naphthyl radical, non substituted or substituted by 1 to 3 substituents and in particular a radical chosen from the following radicals: phenyl, 2-chloro phenyl, 3-chloro phenyl, 3-bromophenyl, 3-(trifluoromethyl) phenyl, 4-chloro phenyl, 4-bromo phenyl, 4-iodo phenyl, 4-(trifluoromethyl) phenyl, 4-nitrophenyl, 4-methoxy phenyl, 4-(difluoromethoxy) phenyl, 4-(trifluoro-methoxy) phenyl, 3-bromo 4-(difluoromethoxy) phenyl, 4-(2,2-dibromo ethenyl) phenyl, 4-ethynyl phenyl, 4-benzyl phenyl, 3,4-dibromo phenyl, 2,4-dichlorophenyl, 3,4-dichloro phenyl, 3,4-difluorophenyl, 3-chloro 4-iodo phenyl, 4-bromo 3-chloro phenyl, 4-bromo 2-fluoro phenyl, 4-bromo 3-fluoro phenyl, 4-bromo 3-(trifluoromethyl) phenyl, 4-chloro 3-(trifluoro-methyl) phenyl, 3,5-bis-(trifluoromethyl) phenyl, 3,4,5-trichloro phenyl, 4-bromo 3,5-dichloro phenyl, 3-phenoxy-phenyl, 4-(fluoro 3-phenoxy) phenyl, 3-bromo 4-(trifluoro-methylsulphonyloxy) phenyl, 3,4-bis (trifluoromethyl-sulphonyloxy) phenyl, 2-naphthyl or 5-bromo 2-naphthyl or 6-bromo 1-napthyl.

In a third preferred variant of the present invention, the steric configuration of Q₁ is such that the Q-(CH₂)_(a) --(X₁)_(b) -- group is in trans position relative to the Q₂ -C(X₂)--N(R₁)(R₂) group.

In a fourth preferred variant of the present invention, Q₁ is non-substituted or substituted by 1 or 2 halogen atoms or by 1 or 2 methyl radicals and in particular a radical chosen from the following radicals: 1,2-cyclopropanediyl, 1-fluoro 1,2-cyclopropanediyl, 1-chloro 1,2-cyclopropanediyl, 1-bromo 1,2-cyclopropanediyl, 1-methyl 1,2-cyclopropanediyl, 3,3-dibromo 1,2-cyclopropanediyl and 1,2-difluoro 1,2-cyclopropanediyl.

In a fifth preferred variant of the present invention, Q₂ represents one of the following radicals: ortho-phenylene, meta-phenylene, para-phenylene, 1,2-naphthylene, 1,3-naphthylene, 1,4-naphthylene, 1,5-naphthylene, 2,5-naphthylene, 4,5-indenylene, 4,6-indenylene, 4,7-indenylene, 4,5-indanylene, 4,6-indanylene, 4,7-indanylene, 1,2,3,4-tetrahydro 5,6-naphthylene, 1,2,3,4-tetrahydro 5,7-naphthylene, 1,2,3,4-tetrahydro 5,8-naphthylene, non-substituted or substituted by 1 to 4 substituants, and in particular the following radicals: 2-methyl 1,4-phenylene, 2,3,5,6-tetrafluoro 1,4-phenylene, 3-methyl 1,4-phenylene, 2-chloro 1,4-phenylene, 2-acetylamino 5-chloro 1,4-phenylene, 2-amino 5-chloro 1,4-phenylene, 2-dimethylamino 5-chloro 1,4-phenylene.

In a sixth preferred variant of the present invention, R₁ represents a branched alkyl radical containing 1 to 6 carbon atoms such as one of the following radicals: isopropyl, isobutyl, 1,2-dimethyl propyl, 1,1,2-trimethyl propyl ou 2,2-dimethyl propyl, 1-methylpropyl, 2-methylbutyl, 2,2-dimethyl 1-methylethyl, 3-chloropropyl, cyclobutyl, cyclohexyl, cyclopropylmethyl, a (2-methyl 1,3-dioxolan 2-yl) methyl radical, or a branched alkenyl radical containing 2 to 5 carbon atoms such as the 2-methyl 2-propenyl, 2-chloro 2-propenyl, 2-bromo 2-propenyl radical or also a non-substituted phenyl radical or a substituted phenyl radical such as one of the following radicals: 2-fluoro phenyl, 2-chloro phenyl, 2-bromo phenyl, 2-iodo phenyl, 2-nitro phenyl, 2-hydroxy phenyl, 2-methoxyphenyl, 2-cyano phenyl, 2-amino phenyl, 2-(dimethylamino) phenyl, 2-(trifluoromethoxy) phenyl, 2-phenoxy phenyl, 2-methoxycarbonyl phenyl, 2-ethoxy-carbonyl phenyl, 2-phenylcarbonylphenyl, 2-formyl phenyl, 2-acetyl phenyl, 2-(methylthio) phenyl, 2-fluorosulphonyl phenyl, 2-ethynyl phenyl, 2-(1-methyl 2-propenyl) phenyl, 2-(hydroxymethyl) phenyl, 2-methyl phenyl, 2-(terbutyl) phenyl, 2-(fluoromethyl) phenyl, 2-(difluoromethyl) phenyl, 2-(trifluoromethyl) phenyl, 2-ethyl phenyl, 2-propyl phenyl, 2-isopropyl phenyl, 2-(pyridin-1-yl) phenyl, 3-chloro phenyl, 3-bromo phenyl, 3-methoxy phenyl, 3-fluoro phenyl, 3-methyl phenyl, 3-phenoxy phenyl, 4-fluoro phenyl, 4-chloro phenyl, 4-cyano phenyl, 4-(cyanomethyl) phenyl, 4-methoxy phenyl, 4-methyl phenyl, 4-(terbutyl) phenyl), 4-(trifluoromethyl) phenyl, 4-phenoxyphenyl, 4-benzyloxyphenyl, 4-methoxy-carbonylphenyl, 4-cyclohexylphenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 2,6-dichlorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxy-phenyl, 3,5-dimethoxyphenyl, 2-methoxy 5-methylphenyl, 2-methoxy 5-trifluoromethyl, 3-methoxy 5-trifluoromethylphenyl, 2-methoxy 5-nitrophenyl, 2-nitro 4-methoxyphenyl, 2-methyl 4-methoxyphenyl, 3,5-dichloro 4-methoxyphenyl, 4,5-dichloro 2-methoxyphenyl, 4-bromo 3,5-dichlorophenyl, 2-(1-methylethyl) phenyl, 3-chloro 2-methyl phenyl, 3-fluoro 2-methyl phenyl, 3-bromo 2-methyl phenyl, 2,3-dichloro phenyl, 2,3-dibromo phenyl, 3,4-dibromo phenyl, 4-fluoro 2-methyl phenyl, 4-chloro 2-fluoro phenyl, 4-fluoro 2-(trifluoromethyl) phenyl, 2,4-difluoro phenyl, 2-chloro 4-methylphenyl, 2-chloro 5-methyl phenyl, 5-chloro 2-methyl phenyl, 5-fluoro 2-methyl phenyl, 5-iodo 2-methyl phenyl, 2,6-difluoro phenyl, 2-fluoro 4-methyl phenyl, 2-fluoro 6-methyl phenyl, 2-chloro 6-methyl phenyl or a radical derived from a heterocycle such as the 2-chloro 3-pyridyl, 3-pyridyl, 2-pyridyl, 4-pyridyl, 2-chloro 3-pyridyl, 3-methyl pyridyl, 5-methyl isoxazol-3-yl, 1,3,4-thiadiazol-2-yl, 4-pyrimidinyl, 3-pyrazolyl, 4-(trifluoro-methyl) thiazol-2-yl, 5-chloro 4-(trifluoromethyl) thiazol-2- yl, 1-piperidinyl, 2,6-dimethyl 1-piperidinyl, 1,4-oxazin-4-yl or 1-perhydroazepinyl radical, or finally R₁ et R₂ represent together with the nitrogen atom to which they are linked a heterocycle such as the 1,4-thiazin-4-yl, 1,4-oxazin-4-yl, 1-aziridinyl, 1-piperidinyl, 1-pyrrolidinyl, 2-methylpiperidin-1-yl, 2-hydroxymethyl-pyrrolidin-1-yl radical.

In a seventh preferred variant of the present invention, R₂ represents a hydrogen atom, an alkyl radical containing 1 to 4 carbon atoms, in particular the ethyl radical, a benzyl radical, an ethoxymethyl radical, a propoxymethyl radical, a group (A) in which X₃ represents an oxygen atom and R₃ represents an alkyl radical containing 1 to 11 carbon atoms, an alkoxycarbonyl radical containing 2 to 5 carbon atoms or a phenoxycarbonyl radical, and R₂ represents in particular in this case, the acetyl hexanoyl, decanoyl, 2-methoxy 2-oxo acetyl, 2-ethoxy 2-oxo acetyl, or 2-phenoxy 2-oxo acetyl radical, a group (B) in which R₃ represents an alkoxy radical containing 1 to 4 carbon atoms and R₂ represents in particular in this case the diethoxyphosphonyl radical, a group (C) in which T₂ represents a bivalent thio radical and R₅ a trifluoromethyl or pentafluoroethyl radical or a phenyl radical non substituted or substituted by one or more halogen atoms or by one or more alkyl radicals containing 1 to 4 carbon atoms, and in this case R₂ represents in particular the trifluoromethylthio, pentafluoroethylthio, or phenylthio, (4-chloro phenyl) thio, (2-methyl phenyl) thio, (4-methyl phenyl) thio or (4-tertbutyl phenyl) thio radical or a group (D) in which j is equal to 0 and R₂ represents in particular in this case the (N-formyl N-methyl amino) thio or (N-methoxycarbonyl N-methyl amino) thio radical.

In an eighth preferred variant, a and b are equal to 0.

In particular a subject of the invention is the compounds whose names follow:

4-(1-fluoro 2-phenyl cyclopropyl) N-isobutyl benzenamide (cis+trans isomers, cis/trans=3/2)

4-(1-fluoro 2-phenyl cyclopropyl) N-(2-methyl phenyl) benzenamide (cis+trans isomers, cis/trans=3/1)

4-[2-(4-chloro phenyl) cyclopropyl] N-isobutyl benzenamide (trans isomer)

4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] N-ethyl N-(2-methyl phenyl) benzenamide (cis isomer)

4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] N-(2-methyl phenyl) benzenamide (cis isomer)

4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] N-isobutyl benzenamide (cis isomer)

4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] N-isobutyl benzenamide (cis isomer)

4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] N-(2-methyl phenyl) benzenamide (cis isomer)

4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] N-isobutyl benzenamide (trans isomer)

4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] N-(2-methyl phenyl) benzenamide (trans isomer)

4-[2-(3,4-dichloro phenyl) 1-fluoro cyclopropyl] N-(2-methyl phenyl) benzenamide (cis isomer)

4-[2-(3,4-dichloro phenyl) 1-fluoro cyclopropyl] N-ethyl N-(2-methyl phenyl) benzenamide (cis isomer)

4-[2-(3,4,5-trichloro phenyl) 1-fluoro cyclopropyl] N-(2-methyl phenyl) benzenamide (cis isomer)

4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] N-methyl N-(2-methyl phenyl) benzenamide (cis isomer)

4-[2-(4-trifluoromethoxy phenyl) 1-fluoro cyclopropyl] N-(2-methyl phenyl) benzenamide (cis isomer)

4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] N-(2,6-dimethyl phenyl) benzenamide (cis isomer)

4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] N-(2,4,6-trimethyl phenyl) benzenamide (cis isomer)

4-[2-(3,4-dichloro phenyl) 1-fluoro cyclopropyl] N-[2-(fluoromethyl) phenyl] benzenamide (cis isomer)

4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] N-(2-methyl phenyl) benzene thioamide (cis isomer)

4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] N-ethyl N-(2 -methyl phenyl) benzene thioamide (cis isomer)

4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] N-(1,4-oxazin-4-yl) benzenamide (cis isomer).

Also a subject of the invention is a preparation process for the compounds of formula (I), characterized in that the acid or corresponding acid derivative of formula (II):

    Q-(CH.sub.2).sub.a -(X.sub.1).sub.b -Q.sub.1 -Q.sub.2 -C(O)-Z(II)

in which Q, a, b, Q₁ and Q₂ are as defined previously and Z represents a hydroxy group, a halogenated group, an alkoxy radical containing 1 to 4 carbon atoms or a -P(O)(Oo)-NHo group, in which o represents a phenyl group, is reacted with an amine of formula (III):

    HN(R.sub.1)(R.sub.2)                                       (III)

in which R₁ and R₂ are as defined previously, in order to obtain a corresponding product of formula (I), in which X₂ represents an oxygen atom, which if necessary, is converted into a product of formula (I) in which (X₂) represents a sulphur atom.

The products of formula (I) obtained according to the above process can be, if appropriate, separated into their optically-active isomers.

The separation of the isomers can be carried out according to methods known to a man skilled in the art for example by photochemical, thermic or chromatographic route.

According to the preferred conditions for implementing the preparation process for the compounds of formula (I) as indicated above, the amidification reaction is in general carried out at a temperature comprised between -25 and +150° C. in an anhydrous and aprotic solvent such as ether, dichloro-methane, toluene or benzene.

The precise reaction conditions also depend on the nature of the Z group; for example when Z represents an alkoxy group, the reaction is carried out at a high temperature for example between 25° and 125° C., in particular 50° C. and preferably in the presence of a trialkylaluminium, such as trimethylaluminium, which forms a complex with the amine of formula (III).

When Z represents a halogenated group, or phosphoro-imidate, the reaction is carried out between 0° and 30° C., in particular at an ordinary temperature and preferably in the presence of a tertiary amine, such as triethylamine. The conversion of an amide into thioamide takes place according to methods known to a man skilled in the art, such as reaction of the amide with phosphorus pentasulphide, hydrogen sulphide, boron trisulphide or thiophosphoryl bromide.

When the derivative of the acid of formula (II) is an acid halide, for example the acid chloride, it is prepared from the acid by reaction with the appropriate reagent such as oxalyl chloride or thionyl chloride. When Z represents a -P(O)(Oo)-NHo group, the corresponding derivative is prepared from the acid by reaction with Cl-P(O)(Oo)-NHo. The acid of formula (II) in which Z represents a hydroxy group can be prepared by hydrolyzing an ester.

The preparation of the compound of formula (II) in which Z represents an alkoxy radical can be carried out in particular:

a) by cyclopropanation of a compound of formula (IV):

    Q-(CH.sub.2).sub.a -(X.sub.1).sub.b -C(R.sub.9)═C(R.sub.10)-Q.sub.2 -C(O)-Z                                                   (IV)

in which Q, a, X₁, b, Q₂ and Z are as defined previously and R₉ and R₁₀ represent, independently of each other, a hydrogen atom, a halogen atom or an alkyl radical, with a carbene generator, such as diazomethane, dibromomethane or diiodo-methane in the presence of diethylzinc;

b) by cyclocondensation of a derivative of formula (V):

    Q-(CH.sub.2).sub.a -(X.sub.1).sub.b -C(R.sub.9)═CH(R.sub.10) (V)

in which Q, a, X₁, b, R₉ and R₁₀ are as defined previously with a compound of formula (VI): ##STR3## to lead to the compound of formula (II) in which Q₁ represents a cyclopropanediyl radical substituted in position 1 by a fluorine atom.

The acid of formula (II) in which Z represents a hydroxy radical can also be prepared by elimination of nitrogen from a compound of formula (VII): ##STR4## to lead to the compound of formula (VIII):

    Q-(CH.sub.2).sub.a -(X.sub.1).sub.b -Q.sub.1 -Q.sub.2 -Hal (VIII)

in which Q, a, X₁, b, Q₂ are as defined previously, Hal represents a bromine or iodine atom and Q₁ represents a non-substituted cyclopropanediyl radical, which product of formula (VIII) is transformed into a cyano derivative of formula (IX):

    Q-(CH.sub.2).sub.a -(X.sub.1).sub.b -Q.sub.1 -Q.sub.2 -C═N (IX)

which is then converted into the corresponding acid of formula (II).

The compound of formula (VII) is prepared by reaction of hydrazine with the compound of formula (X): ##STR5## the compound of formula (X) is prepared by condensation in a basic medium of a compound of formula (XI):

    Q-(CH.sub.2).sub.a -(X.sub.1).sub.b --CO--CH.sub.3         (XI)

with an aromatic aldehyde of formula (XII):

    Hal-Q.sub.2 -CHO                                           (XII)

which products of formulae (XI) and (XII) are either commercially-available or easily synthesizable by a man skilled in the art.

The compound of formula (VI) is prepared by bromination of a compound of formula (XIII):

    F-CH.sub.2 -Q.sub.2 -COZ                                   (XIII)

which itself is prepared from a compound of formula (XIV):

    HO--CH.sub.2 -Q.sub.2 -COZ                                 (XIV)

which is commercially-available or easily synthesizable by a man skilled in the art.

The compounds of formulae (IV) and (V) are known or can be obtained according to the usual methods known to a man skilled in the art.

The experimental conditions are illustrated by the examples described in the present Application.

Also a subject of the invention is the compounds of formulae (II) , (VI), (VII) , (VIII), (IX) and (X) with the exception of-the products whose names follow:

methyl 5-(2-phenyl cyclopropyl) 2-acetoxy benzoate

methyl 2-(2-phenyl cyclopropyl) benzoate

1,2-diphenyl cyclopropane 4,4'di carbonitrile

4-[2-(1-naphthyl) cyclopropyl] benzonitrile and

3-(4-bromo phenyl) 1-phenyl propenone

and with the exception of the products of formula (VIII) in which X₁ represents a sulphonyl group.

The compounds of formula (I) can be used for combating harmful organisms such as arthropods, for example insects and acarids, and helminths, for example nematodes, or molluscs, for example slugs. Therefore a subject of the present invention is a process for combating arthropods and/or helminths and/or molluscs, which includes the administration to arthropods and/or helminths and/or molluscs or to their environment of a sufficient quantity of a compound of formula (I) to destroy the harmful organism. A subject of the present invention is also a process for combating and/or eradicating infestations by arthropods and/or helminths and/or molluscs in animals (including human beings) and/or plants (including trees) and/or stored products, which includes the administration to the animal or site of an effective quantity of a compound of formula (I). A subject of the invention is also the compounds of formula (I) for use in human and veterinary medicine, in public health and/or in agriculture to combat harmful arthropods and/or helminths.

The compounds of formula (I) are particularly valuable for the protection of standing crops, fodder plants, plantations, greenhouse crops, orchards and vineyards, ornamental plants and trees in plantations and in forests, for example cereals (such as corn, wheat, rice and sorghum), cotton, tobacco, legumes and salad plants (such as beans, cabbages, curcubitacae, lettuces, onions, tomatoes and sweet peppers), food crops (for example potatoes, sugar beet, groundnuts, soya and rape), sugar cane, grasslands and fodder crops (such as corn, sorghum and alfalfa), plantations (such as those producing tea, coffee, cocoa, bananas, palm oil, coconuts, rubber and spices), orchards and planted woods (such as those producing stone fruits and pomaceous fruits, citrus fruits, kiwis, avocadoes, mangoes, olives and nuts), vines, ornamental plants, flowers and bushes grown in greenhouses and in gardens and parks, forest trees (both deciduous and evergreen) in forests, plantations and nurseries.

They are also invaluable for the protection of timber (standing, felled, processed, stored or in building) against attack by sirex (for example Urocerus), coleoptera (for example scolytidae, platypodidae, lyctidae, bostrychidae, cerambucidae and anobiidae) and termites.

They are used for the protection of stored products, such as grains, fruits, nuts, spices and tobacco, in the whole state, powdered or converted into products, against attack by mites, coleoptera and weevils. They also protect stored animal products, such as skins, furs, wool and feathers, in a natural or converted form (for example as carpets or textile materials), against attack by mites and coleoptera, as well as for meat and fish against attack by coleoptera and flies.

The compounds of general formula (I) are of particular use for combating the arthropods, helminths or molluscs which are harmful to man and domestic animals or are propagators or vectors of illnesses affecting the latter, for example those described above, more especially in the area of combating ticks, mites, lice, fleas, midges and flies, which cause bites and are a nuisance.

In particular the invention relates to the use of the the compounds of formula (I) as defined previously, as a pesticide in particular as insecticides, acaricides and nematicides in the protection of crops, in particular rice and cotton crops, or for the treatment of premises for storing products of said crops and in particular as an insecticide or acaricide in domestic or public premises.

The compounds of formula (I) can be used to such ends by the use of the compounds as they are or in diluted form in a known manner as a bath, spray, drift, varnish, foam, powder, dusting powder, aqueous suspension, paste, gel, shampoo, ointment, combustible solid, vaporization mat, combustible coil, bait, food supplement, wettable powder, granules, aerosol, emulsifiable concentrates, oily suspensions, oily solutions, pressurized spray, impregnated article, lotion or other standard compositions well known to a man skilled in the art. The bath concentrates are not used as they are, but diluted with water and the animals are immersed in a tank containing the bath. The sprays can be applied by hand or using a spraying lance or spraying boom. The animal, the soil, the plant or the surface can be saturated with the spray by application in high volume or be superficially covered with the spray by the application of a small or ultrasmall volume. The aqueous suspensions can be applied to the animal in the same way as the sprays and the baths. The dusting powders can be distributed by means of a powder applicator or, in the case of animals, be incorporated in perforated bags attached to trees or to poles. The pastes, shampoos and ointments can be applied by hand or distributed over the surface of an inert material against which the animals rub themselves and thus transfer the material onto their skin. The lotions are distributed in the form of a small volume dose of liquid on the back of the animals, so that all or the majority of the liquid remains on the animals.

The compounds of formula (I) can be presented as compositions which are ready to use on plants, animals and surfaces or as compositions which have to be diluted before use, but the compositions of both types contain a compound of formula (I) in an intimate mixture with one or more excipients or diluting agents. The excipients can be liquid, solid or gaseous or can contain mixtures of such substances and the compound of formula (I) can be present at a concentration of 99 to 0.025% w/v, depending on whether the composition must be more or less diluted.

The dusting powders, powders and granules contain the compound of formula (I) in an intimate mixture with a pulverulent inert solid excipient, for example appropriate clays, kaolin, bentonite, attapulgite, adsorbant carbon black, talc, mica, chalk, gypsum, tricalcium phosphate, powdered cork, magnesium silicate, plant excipients, starch and diatomaceous earth. These solid compositions are generally prepared by impregnating the solid diluting agents with solutions of the compound of formula (I) in volatile solvents, by evaporatng the solvents and, if desired, by grinding up the products in order to obtain powders and, if desired, by granulating, by pressing or by encapsulating the products.

The sprays of a compound of formula (I) can contain a solution in an organic solvent (for example those set out below) or an emulsion in water (bath or shower) prepared on site from an emulsifiable concentrate (also called oil miscible in water), which can also serve for the immersion. The concentrate preferably contains a mixture of the active constituent, with or without an organic solvent and one or more emulsifying agents. The solvents can be present within wide limits, but preferably in a quantity of 0 to 90% w/v of the composition and can be chosen from kerosene, ketones, alcohols, xylene, aromatic naphtha and other known solvents for use in compositions. The concentration of emulsifying agents can vary within wide limits, but is preferably situated within the range 5 to 25% w/v and the emulsifying agents are advantageously non-ionic surfactants, in particular polyoxy-alkylenic esters of alkylphenols and polyoxyethylenic derivatives of hexitol anhydrides, or anionic surfactants, in particular sodium laurylsulphate, ether sulphates of fatty alcohols, sodium and calcium salts of alkylarylsulphonates and alkylsulphosuccinates.

The cationic emulsifying agents are in particular benzalkonium chloride and quaternary ammonium ethosulphates.

The amphoteric emulsifying agents are in particular carboxymethylated oleic imidazoline and the alkyl dimethylbetaines.

The vaporisation mats normally contain a mixture of cotton and cellulose pressed into a plate of about 32 mm by 22 mm by 3 mm treated with a quantity of up to 0.3 ml of a concentrate which contains the active constituent in an organic solvent and optionally an anti-oxidant, a colouring agent and a perfume.

The insecticide is vaporized by a heat source, such as an electrical heating apparatus for mats.

The combustible solids normally contain sawdust and a binding aqent in a mixture with the active ingredient and shaped into strips (normally as a coil). A colouring agent and a fungicide can also be added.

The wettable powders contain an inert solid excipient, one or more surfactants and optionally stabilizing agents and/or anti-oxidants.

The emulsifiable concentrates contain emulsifying agents and often an organic solvent such as kerosene, ketones, alcohols, xylenes, aromatic naphtha and other known solvents.

The wettable powders and emulsifiable concentrates normally contain 5 to 95% by weight of the active ingredient and are diluted before use, for example with water.

The varnishes contain a solution of the active ingredient in an organic solvent, together with a resin and optionally a plasticizer.

The baths can be prepared not only from emulsifiable concentrates, but also from wettable powders, baths based on soap and aqueous suspensions containing a compound of formula (I) in an intimate mixture with a dispersing agent and one or more surfactants.

The aqueous suspensions of a compound of formula (I) can contain a suspension in water together with a suspension agent, stabilizers or other agent. The suspensions or solutions can be used as they are or in a form diluted in a known manner.

The ointments (or greases) can be prepared from vegetable oils, synthetic esters of fatty acids or lanoline, together with an inert base such as soft paraffin. A compound of formula (I) is preferably evenly distributed in the mixture in solution or suspension. The ointments can also be obtained from emulsifiable concentrates by dilution of the latter in an ointment base.

The pastes and shampoos are also semi-solid compositions in which a compound of formula (I) can be present as a uniform dispersion in an appropriate base, such as liquid or soft paraffin, or in a non-fatty base with glycerol, glue or a suitable soap. Due to the fact that the ointments, shampoos and pastes are usually applied without further dilution, they must contain the appropriate percentage of the compound of formula (I) required for the treatment.

The aerosol sprays can be prepared as a simple solution of the active ingredient in the aerosol propellant and a cosolvant such as a halogenated alkane and the solvents mentioned above, respectively. The lotion compositions can be presented as a solution or suspension of a compound of formula (I) in a liquid medium. A bird or mammal host can also be protected against infestation by ectoparasitic acarids by carrying a manufactured product fashioned in a suitably moulded plastic material which is impregnated with a compound of formula (I). These manufactured products include collars, ear tags, bands, cloths and strips suitably attached on the appropriate part of the body. The plastic material is advantageously a poly (vinyl chloride).

Therefore a particular subject of the invention is a composition containing:

a) a compound of formula (I) as defined previously,

b) inert excipients suitable for the use as pesticides of said product of formula (I), a composition containing:

a) a compound of formula (I) as defined previously,

b) inert excipients suitable for the use in veterinary field of said product of formula (I),

and a compound of formula (I) as defined previously, for the implementation of a treatment method for the human or animal body characterized in that a pharmaceutically acceptable formulation of said compound is applied to said body.

The compounds of formula (I) are for use in the protection and the treatment of plant species, in which case an effective insecticide, acaricide, molluscide, nematocide quantity of the active ingredient is applied. The applied dose varies according to the compound chosen, the nature of the composition, the application method, the type of plant, the density of planting, the probable infestation and various other factors, but in general a dose suitable for agriculture is situated in the range 0.001 to 3 kg per hectare and preferably between 0.01 and 1 kg per hectare. The typical compositions for agricultural use contain between 0.0001% and 50% of a compound of formula (I) and advantageously between 0.1 and 15% by weight of a compound of formula (I).

The concentration of the compound of formula (I) for use on an animal, premises or outside locations varies according to the compound chosen, the interval between treatments, the nature of the composition and the probable infestation, but in general the compound must be contained in the composition applied in a quantity of 0.001 to 20.0% w/v, preferably 0.01 to 10% w/v. The quantity of the compound deposited on an animal varies according to the application method, the size of the animal, the concentration of the compound in the composition applied, the dilution factor of the composition and the nature of the composition, but is generally situated in the range 0.0001% to 0.5% w/w, except for the non-diluted compositions, such as the lotion compositions which are generally deposited at a concentration in the range 0.1 to 20.0% and preferably 0.1 to 10%. The quantity of compound to be applied to stored products is generally situates in the range 0.1 to 20 ppm. Sprayings in opens spaces can be carried out so as to produce an average initial concentration of 0.001 to 1 mg of the compound of formula (I) per m³ of treated area.

The ointments, greases, pastes and aerosols are usually applied randomly as described above and concentrations of 0.001 to 20% w/v of a compound of formula (I) in the applied composition can be used.

The compounds of formula (I) have been shown to have an activity against the house-fly (Musca domestica). In addition, some compounds of formula (I) have an activity against other harmful arthropods, in particular Myzus persicae, Tetranychus urticae, Spodoptera littoralis, Heliotuis virescens, Plutella xylostella, Culex spp., Tribolium castaneum, Sitophilus granarius, Periplaneta americana and Blattella germanica. The compounds of formula (I) are therefore useful for combating arthropods, for example insects and acarids, in any environment where they constitute a nuisance, for example in agriculture, in breeding, in public health and in the domestic environment.

The harmful insects are in particular members of the orders of coleoptera (for example Anobium, Ceuthorrhynchus, Rhynchophorus, Cosmopolites, Lissorhoptrus, Meligethes, Hypothenemus, Hylesinus, Acalymma, Lema, Psylliodes, Leptinotarsa, Gonocephalum, Agriotes, Dermolepida, Heteronychus, Phaedon, Tribolium, Sitophilus, Diabrotica, Anthonomus or Anthrenus spp.), lepidoptera (for example Ephestia, Mamestra, Earias, Pectinophora, Ostrinia, Trichloplusia, Pieris, Laphygma, Agrotis, Amathes, Wiseana, Tryporyza, Diatraea, Sparganothis, Cydia, Archips, Plutella, Chilo, Heliothis, Spodoptera littoralis, Helrotuis virescens, Spodoptera or Tineola spp.), diptera (for example Musca, Aedes, Anopheles, Culex, Glossina, Simulium, Stomoxys, Haematobia, Tabanus, Hydrotaea, Lucilia, Chrysomyia, Callitroga, Dermatobia, Gasterophilus, Hypoderma, Hylemyia, Atherigona, Chlorops, Phytomyza, Ceratitis, Liriomyza and Melophagus spp.), phthiraptera (Mallophaga, for example Damalina spp., and Anoplura, for example Linognathus and Haematopinus spp.), hemiptera (for example Aphis, Bemisia, Phorodon, Aeneolamia, Empoasca, Parkinsiella, Pyrilla, Aonidiella, Coccus, Pseudococcus, Helopeltis, Lygus, Dysdercus, Oxycarenus, Nezara, Aleyrodes, Triatoma, Psylla, Myzus, Megoura, Phylloxera, Adelges, Nilaparvata, Nephotettix or Cimwx spp.), orthoptera (for example Locusta, Gryllus, Schistocerca or Acheta spp.), dictyoptera (for example Blattella, Periplaneta or Blatta spp.), hymenoptera (for example Athalia, Cephus, Atta, Solenopsis or Monomorium spp.); isoptera (for example Odontotermes and Reticulitermes spp.), siphonaptera (for example Ctenocephalides or Pulex spp.), thysanura (for example Lepisma spp.), dermaptera (for example Forficula spp.) and psocoptera (for example Peripsocus spp.) and thysanoptera (for example Thrips tabaci).

The harmful acarids are notably ticks, for example members of genus Boophilus, Ornithodorus, Rhipicephalus, Amblyomma, Hyalomma, Ixodes, Haemaphysalis, Dermacentor and Anocentor, and mites and scabies mites such as Acarus, Tetranychus, Psoroptes, Notoednes, Sarcoptes, Psorergates, Chorioptes, Eutrombicula, Demodex, Panonychus, Bryobia, Eriophyes, Blaniulus, Polyphagotarsonemus, Scutigerella and Oniscus spp.

The nematodes which attack plants and trees which are important in agriculture, forestry and horticulture, both directly and by propagating bacterial, viral, mycoplasmic or fungal diseases of plants, are in particular the root scab nematodes, such as Meloidogyne spp. (for example M. incognita); the nematodes of roots, such as Globodera spp. (for example G. rostochiensis); Heterodera spp. (for example H. avenae); Radopholus spp. (for example R. similis); the nematodes of grasslands, such as Pratylenchus spp. (for example P. pratensis); Belonolaimus spp (for example B. gracilis); Tylenchulus spp. (for example T. semipenetrans); Rotylenchulus spp. (for example R. reniformis); Rotylenchus spp. (for example R. robustus); Helicotylenchus spp. (for example H. multicinctus); Hemicycliophora spp. (for example H. gracilis); Criconemoides spp. (for example C. similis); Trichodorus spp. (for example T. primitivus); the xiphophore nematodes, such as Xiphinema spp. (for example X. diversicaudatum), Longidorus spp. (for example L. elongatus); Hoplolaimus spp. (for example H. coronatus); Aphelenchoides spp. (for example A. ritzemabosi, A. besseyi); and the nematodes of bulbs, such as Ditylenchus spp. (for example D dipsaci).

The compounds of the invention can be combined with one or more other active pesticide constituents (for example the pyrethroids, carbamates and organophosphates) and/or with attractants, repellents, bactericides, fungicides, nematocides, vermifuges and so on. In addition, it has been observed that the activity of the compounds of the invention can be increased by the addition of a synergist or potentialization agent, for example a synergist of the class of oxydase inhibitors, such as piperonylbutoxide or propyl 2-propynylphenyl phosphonate, by the addition of a second compound of the invention or a pesticide pyrethroid. When an oxydase inhibitor synergist is present in a composition of the invention, the ratio of the synergist to the compound of formula (I) is situated in the range 25:1 to 1:25, for example at approximately 10:1.

The stabilizing agents to prevent any chemical degradation which the compounds of the invention may undergo are in particular, for example, anti-oxidants (such as tocopherols, butylhydroxyanisole, butylhydroxytoluene), vitamin C (ascorbic acid) and oxygen collectors (such as epichlorhydrin), as well as organic and inorganic bases, for example of the trialkylamines such as triethylamine, which can act as basic stabilising agents and collectors.

The compounds of the present invention have pesticide properties and/or an increased photostability and/or a reduced toxicity for mammals.

The following examples illustrate the preferred aspects of the invention in a non-limitative manner.

Preparation 1: 4-(1-fluoro 2-phenyl cyclopropyl) benzoic acid, racemic cis isomer (A)+racemic cis+trans mixture (50/50) (B)

Stage A: tert-butylate 4-formyl benzoate

a) 4-formyl benzoic acid chloride

15 g of commercial 4-formyl benzoic acid and 200 cm³ of dichloromethane are mixed together at 0°C. under an inert gas atmosphere, then 9 cm³ of commercial oxalyl chloride and 0.2 cm³ of dimethylformamide are added, the reaction medium is left for half an hour at 0° C. then for 20 hours at ambient temperature, the acid chloride obtained is brought to dryness.

b) tert-butylate 4-formyl benzoate

20 cm³ of tert-butanol and 100 cm³ of pyridine are mixed together at 6° C. under an inert gas atmosphere, then a solution of the residue obtained in Stage a) in 200 cm³ of dimethylformamide is introduced, after one hour at ambient temperature, the reaction medium is heated under reflux for 4 hours then left to return to ambient temperature, the solvent is driven off, the residue is taken up in ethyl acetate, followed by washing and chromatographing on silica. In this way the tert-butyl ester is obtained with a yield of 48.5%. TLC: R_(f) =0.3 (eluant: heptane--ethyl acetate (8-2)).

Stage B: tert-butyl 4-(hydroxymethyl) benzoate

5.23 g of tert-butyl 4-formyl benzoate obtained according to Stage A is mixed with 100 cm³ of tetrahydrofuran and the mixture is cooled down to 0° C.; 1 g of sodium borohydride is then added, the temperature is left to rise to 20-25° C., agitation is carried out for 3 hours, followed by hydrolysis with 100 cm³ of a 10% aqueous solution of ammonium chloride, extraction with ethyl acetate, the extracts are washed, dried, brought to dryness and the residue is chromatographed on silica (eluant: heptane - ethyl acetate (1--1)).

In this way 5 g of the expected hydroxymethylated derivative is isolated.TLC: R_(f) =0.3 (eluant: heptane--ethyl acetate (1--1)).

Microanalysis: C₁₂ H₁₆ O₃ =208.3

    ______________________________________                                                        C %  H %                                                        ______________________________________                                         Calculated       69.2   7.7                                                      Found 68.9 7.8                                                               ______________________________________                                    

NMR of the proton in CDCl₃ at 250 MHz (in ppm) 1.59 (s): CO₂ tBu; 2.01 (t): φ--CH₂ --OH; 4.75 (d): φ--CH₂ --OH 7.40 and 7.96 (AA'BB'): aromatic H's. IR in CHCl₃ in cm⁻¹ 3610: OH; 1708: C═O ester; 1613-1576-1505: aromatics.

Stage C: tert-butyl 4-(fluoromethyl) benzoate

4.5 g of tert-butyl 4-(hydroxymethyl) benzoate obtained according to Stage B is mixed with 100 cm³ of dichloro-methane under an inert gas atmosphere and the mixture is cooled down to 0° C. 3.56 g of commercial diethylaminosulphur trifluoride (C₂ H₅)₂ NSF₃ known by the abbreviation DAST is then added, the reaction medium is agitated for one hour at 0°/+5° C., then for one hour at 20-25° C., poured into a 10% aqueous solution of sodium bicarbonate, extraction is carried out with dichloromethane, the extracts are dried, brought to dryness and the residue is chromatographed on silica (eluant: methylene chloride). 3 g of the expected fluoromethylated derivative is isolated.

TLC: R_(f) =0.37 (eluant: heptane--ethyl acetate (8-2)).

Microanalysis for C₁₂ H₁₅ FO₂ =210.25

    ______________________________________                                                  C %        H %    F %                                                 ______________________________________                                         Calculated 68.6         7.2    9.0                                               Found 68.3 7.3 9.1                                                           ______________________________________                                    

NMR of the proton in CDCl₃ at 250 MHz (in ppm) 1.60 (s): CO₂ tBu; 5.43 (d, J=47): CH₂ --F; 7.40 and 8.01 (AA'BB'): aromatic H's. IR in CHCl₃ in cm⁻¹ 1712: C═O ester; 1618-1582-1512: aromatics.

Stage D: tert-butyl 4-(bromofluoro methyl) benzoate 2.3 g of tert-butyl 4-(fluoromethyl) benzoate obtained according to Stage C is mixed with 30 cm³ of tetrachloro-methane. 0.1 g of commercial 2,2-azobisisobutyronitrile known by the abbreviation AIBN and 2 g of N-bromo succinimide are added to the mixture, then the whole is taken to reflux and irradiated for 4 hours, a further 0.2 g of AIBN is added, irradiation is carried out for another 4 hours, then the reaction medium is left at rest for 48 hours at ambient temperature. After filtration and chromatography on silica, 1.7 g of the expected bromofluorinated derivative is obtained.

Melting point: 39.4° C. TLC: R_(f) =0.32 (eluant: heptane--dichloromethane--tert-butyl methyl ether (90-5-5)).

Microanalysis for C₁₂ H₁₄ BrFO₂ =289.15

    ______________________________________                                                   C %  H %        Br %   F %                                           ______________________________________                                         Calculated  49.85  4.9        27.6 6.6                                           Found 50.0   4.9 27.4 6.9                                                    ______________________________________                                    

NMR of the proton in CDCl₃ at 250 MHz (in ppm) 1.6 (s): CO₂ tBu; 7.43 (d, J=49.5): CHBrF; 7.53-8.04 (AA'BB'): aromatic H's. IR in CHCl₃ in cm⁻¹ 1711: C═O ester; 1613-1580-1506: aromatics.

Stage E: (±) tert-butyl 4-(1-fluoro 2-phenyl cyclopropyl) benzoate (cis isomer)

30 cm³ of tetrahydrofuran, 2.2 g of potassium tert-butylate and 4 cm³ of commercial styrene are mixed together under an inert gas atmosphere, then a solution of 3 g of tert-butyl 4-(bromo fluoromethyl) benzoate, obtained according to Stage D, in 30 cm³ of tetrahydrofuran, is added over half an hour; a quarter of an hour later the mixture is poured into a 10% aqueous solution of ammonium chloride, the whole is extracted with ethyl acetate, the extracts are washed, dried, brought to dryness and the residue is chromatographed. Thus 0.25 g of the expected product is obtained.

Melting point: 57.4° C. TLC: R_(f) =0.15 (eluant: heptane-toluene (50--50))

Microanalysis for C₂₀ H₂₁ FO₂ =312.4

    ______________________________________                                                  C %        H %    F. %                                                ______________________________________                                         Calculated 76.9         6.8    6.1                                               Found 76.8 6.7 5.9                                                           ______________________________________                                    

NMR of the proton in CDCl₃ at 250 MHz (in ppm) 1.6 (s): C0₂ tBu; 1.5 and 2.0 (m) CH₂ in position 3 of the cyclopropane; 2.51 (m): CH in position 2 of the cyclopropane (in trans/F position); 7.31 (m), 8.0 (wd): H of the phenylene; 7.31 (m): H of the phenyl.

IR in CHCl₃ in cm⁻¹ 1370; 1707: CO₂ tBu; 1614, 1606, 1575, 1511, 1500: φ. MS: M⁺ =312⁺

By operating in an analogous manner, the following isomer compound mixture was also obtained:

tert-butyl 4-(1-fluoro 2-phenyl cyclopropyl) benzoate (cis+trans isomers; cis/trans=70/30), racemic.

Stare F: 4-(1-fluoro 2-phenyl cyclopropyl) benzoic acid (cis+trans isomers; cis/trans=70/30), racemic

1 g of tert-butyl 4-(1-fluoro 2-phenyl cyclopropyl) benzoate cis/trans=70/30 racemic obtained according to Stage E is mixed with 80 cm³ of toluene; 0.09 mg para-toluenesulphonic acid monohydrate is added to the mixture, the whole is heated for 6 hours at 100° C. then left at rest overnight. After washing, extraction with ethyl acetate, drying and evaporation to dryness, 1 g of a white solid is obtained (cis/trans isomer=70/30, racemic).

Stage G: 4-(1-fluoro 2-phenyl cyclopropyl) benzoic acid, racemic cis isomer (A)+mixture racemic cis+racemic trans (50/50) (B)

The gram of white solid obtained above is recrystallized from isopropyl ether. 0.39 g of the racemic pure cis isomer (A) is obtained which precipitates and 0.5 g of the cis/trans mixture (50/50) (B) is obtained after having brought the mother liquors to dryness.

Analysis of isomer (A)

Melting point: 169.2° C.

Microanalysis for C₁₆ H₁₃ FO₂ =256.3

    ______________________________________                                                  C %        H %    F %                                                 ______________________________________                                         Calculated 75.0         5.1    7.4                                               Found 74.7 5.0 7.3                                                           ______________________________________                                    

NMR of the proton in CDCl₃ at 250 MHz (in ppm) 1.83 (m) and 2.04 (m): CH₂ in position 3 of the cyclopropane; 2.57 (m): CH in position 2 of the cyclopropane; 7.39 and 8.14 (AA',BB'): H of the phenylene group; 7.35 to 7.4 (m): H of the phenyl group.

IR in CHCl₃ in cm⁻¹ 1725 and 1694: C═O; 1615, 1575, 1512 and 1500: φ.

MS: M⁺ =312⁺

EXAMPLE 1 4-(1-fluoro 2-phenyl cyclopropyl) N-isobutyl benzenamide (cis+trans isomers, cis/trans=3/2)

Stage A: preparation of the 4-(1-fluoro 2-phenyl cyclopropyl) benzoic acid chloride

0.35 g of 4-(1-fluoro 2-phenyl cyclopropyl) benzoic acid (mixture (B)), obtained according to Preparation 1, and 20 cm³ of dichloromethane are mixed together under an inert gas atmosphere, the mixture is cooled down to 0° C., 0.207 g of commercial oxalyl chloride and 0.01 cm³ of dimethylformamide are added, the whole is agitated for 3 hours at 20-250° C. and brought to dryness in order to collect the acid chloride.

Stage B: Amidification

10 cm³ of pyridine and 0.2 cm³ of commercial isobutyl-amine are mixed together under an inert gas atmosphere, the mixture is cooled down to 0° C. then a solution of acid chloride obtained in Stage A in 4 cm³ of dimethylformamide is added; the reaction medium is agitated for 20 hours at 20-25° C., brought to dryness, purified and recrystallized from isopropyl ether in order to isolate 0.3 g of the expected amide.

Melting point: 100° C.

TLC: R_(f) =0.2-0.25 (eluant: heptane-dichloromethane-tert-butyl methyl ether (5-4-1)).

Microanalysis for C₂₀ H₂₂ FNO=311.14

    ______________________________________                                                   C %  H %        F %    N %                                           ______________________________________                                         Calculated  77.1   7.1        6.1  4.5                                           Found 77.0 7.1 6.2 4.5                                                       ______________________________________                                    

NMR of the proton in CDCl₃ (in ppm) mixture of cis (A) and trans (B) isomers

(A)

0.95 and 0.99 (d): CH₃ of the isobutyl; 1.68 to 2.10: CH of the isobutyl and CH₂ in position 3 of the cyclopropyl; 2.51 (m): CH in position 2 of the cyclopropyl; 3.23: CH₂ of the isobutyl; 6.07: NH; 6.95 to 7.36: H of the phenyl group; 7.58 (d) and 7.79 (d): H of the phenylene group.

(B)

3.04 (d,d,d, J=8.5-11.5 and 20): CH in position 2 of the cyclopropyl; 3.30: CH₂ of the isobutyl; 6.18: NH.

IR in CHCl₃ in cm⁻¹ 3465: =C-NH; 1656: C═O; 1616, 1572, 1530 and 1502: φ.

MS: M⁺ =311⁺

EXAMPLE 2 4-(1-fluoro 2-phenyl cyclopropyl) N-(2-methyl phenyl) benzenamide (cis+trans isomers, cis/trans=3/1)

Stage A: Preparation of the intermediate acid chloride

0.15 g of the isomer mixture (B) and 0.20 g of the cis isomer (A) of 4-(1-fluoro 2-phenyl cyclopropyl) benzoic acid, obtained according to Preparation 1, and 20 cm³ of dichloro-methane, are mixed together under an inert gas atmosphere, the mixture is cooled down to 0° C., then 0.15 cm³ of oxalyl chloride and 0.01 cm³ of dimethylformamide are added to the mixture, agitation is carried out for 3 hours at ambient temperature and the reaction medium is brought to dryness under vacuum in order to collect the acid chloride.

Stage B: Amidification

10 cm³ of pyridine and 0.15 cm³ of commercial ortho-toluidine are mixed together under an inert gas atmosphere and the mixture is cooled down to 0° C. and a solution of the acid chloride obtained in Stage A in 6 cm³ of dimethyl-formamide is added; the reaction medium is agitated for 24 hours at ambient temperature, brought to dryness and chromatographed on silica in order to obtain 0.43 g of the expected amide.

Melting point: 138.2° C.

TLC: R_(f) =0.3-0.35 (eluant: heptane-dichloromethane-tert-butyl methyl ether (5-4-1)).

Microanalysis for C₂₃ H₂₀ FNO=345.4

    ______________________________________                                                   C %  H %        F %    N %                                           ______________________________________                                         Calculated  80.0   5.8        5.5  4.1                                           Found 79.9 5.9 5.4 4.0                                                       ______________________________________                                    

NMR of the proton in CDCl₃ at 250 MHz (in ppm) mixture of cis (A) 75% and trans (B) 25% isomers For both isomers 1.70 to 1.87 and 1.93 to 2.10: CH₂ in position 3 of the cyclopropane, 6.95 to 8.00: aromatic H's and NH.

For (A):

2.35 (s): CH₃ of the φ-CH₃ ; 2.55 (m): CH in position 2 of the cyclopropane, for (B):

2.30 (s): CH₃ of the φ-CH₃ ; 3.08 (d,d,d; J=8, 5, 11 and 20):

CH in position 2 of the cyclopropane,

IR in CHCl₃ in cm⁻¹ 3440: ═C--NH; 1677: >C═O; 1614, 1605, 1589, 1571, 1526, 1510 and 1500: φ.

MS: MH⁺ =346⁺

Preparation 3: 4-[2-(4-chloro phenyl) cyclopropyl] benzoic acid (trans isomer)

Stage A: 3-(4-bromo phenyl) 1-(4-chloro phenyl) propenone

A mixture prepared from 15.46 g of commercial 4-chloro-acetophenone, 18.5 g of 4-bromo benzaldehyde and 75 cm3 of 100% ethanol is heated to 35° C., then after a quarter of an hour a solution of 7.41 g of sodium hydroxide in 37 cm³ of water is added, and the whole is agitated overnight. After filtering and rinsing, 33 g of the expected product is obtained.

TLC: R_(f) =0.65 (eluant: hexane-ethyl acetate (1-1))

Stage B: 5-(4-bromo phenyl) 3-(4-chloro phenyl) 4,5-dihydro pyrazole

25 g of 3-(4-bromo phenyl) 1-(4-chloro phenyl) propenone, obtained according to Stage A, 50 cm³ of hydrazine hydrate and 8 cm³ of water are mixed together, the mixture is taken to reflux for one and a half hours then cooled down to ambient temperature, 200 cm³ of water is added and the precipitate obtained is washed.

Stage C: 1-(4-bromo phenyl) 2-(4-chloro phenyl) cyclopropane (trans isomer)

50 cm³ of diethylene glycol and 2.72 g of potassium hydroxide are added to the crude product obtained according to Stage B, the reaction medium is heated at 240° C. for one and a half hours, then cooled down and poured into water, extraction is carried out with diethyl ether, the extracts are dried and brought to dryness and the residue is chromatographed, in order to obtain, after recrystallization, 7.5 g of the expected product.

Stage D: 4-[2-(4-chloro phenyl) cyclopropyl] benzonitrile

2.0 g of the brominated derivative obtained according to Stage C, cm³ of commercial N-methyl pyrrolidine and 1.17 g of cuprous chloride are mixed together, the mixture is taken to reflux for 24 hours, cooled down to 20° C., extraction is carried out with ethyl ether, the extracts are dried, brought to dryness and the residue is chromatographed on silica. 0.8 g of the expected product is collected.

TLC: R_(f) =0.53 (eluant: ethyl ether-hexane (1-13 1))

MS: M⁺ =254⁺

Stage E: 4-[2-(4-chloro phenyl) cyclopropyl] benzoic acid (trans isomer)

0.4 g of the cyanated derivative obtained according to Stage D, 7.5 cm³ of ethanol and 7.5 cm³ of a 10M aqueous solution of sodium hydroxide are mixed together, the mixture is taken to reflux for 12 hours, poured into water, washed, acidified with hydrochloric acid, extracted with ethyl ether, the extracts are dried, brought to dryness and 0.3 g of the expected acid is obtained.

TLC: R_(f) =0.37 (eluant: ethyl ether)

EXAMPLE 3 4-[2-(4-chloro phenyl) cyclopropyl] N-isobutyl benzenamide (trans isomer)

0.3 g of the product obtained according to Preparation 3 is mixed with 5 cm³ of dichloromethane, then 0.1 cm³ of oxalyl chloride and a drop of dimethylformamide are added, agitation is carried out for 2 hours, followed by bringing to dryness, 5 cm³ of dichloromethane is added, the reaction medium is cooled down to -10° C. and 0.1 cm³ of pyridine, 0.1 cm³ of isobutylamine, 5 mg of dimethylaminopyridine and 2 cm³ of dichloromethane are added, and the whole is agitated for one hour at ambient temperature. The reaction medium is then poured into water, followed by washing, drying, filtering then bringing to dryness and purifying.

0.23 g of the expected product is obtained.

Melting point: 136-138° C.

TLC: R_(f) =0.46 (eluant: ethyl ether).

NMR of the proton in CDCl₃ at 250 MHz 0.96 (d): CH₃ of the isobutyl; 1.52 (m) and 2.16 (m): CH in position 1 and 2 and CH₂ in position 3 of the cyclopropyl; 1.80-2.08 (m): CH of the isobutyl; 3.24 (t): CH₂ of the isobutyl; 6.15: NH; 7.06 (d), 7.18 (d), 7.25 (d), 7.71 (d): aromatic H's.

MS: M⁺ =328⁺

Preparation 4: 4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] benzoic acid (cis isomer)

Stage A: tert-butyl 4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] benzoate (cis+trans isomers; cis/trans=37/63), racemic,

By operating as in Stage E of Preparation 1, using commercial 4-chloro styrene, the desired product is obtained.

Melting point: 110° C. cis product

TLC: cis product 0.5-0.27 (eluant: hexane-toluene (50-50)) trans product 0.27-0.30 (eluant: hexane-toluene (50-50))

NMR of the proton at 250 MHz (in ppm) cis product 2.4-2.45: CH in position 2 of the cyclopropane trans product 3.0-3.05: CH in position 2 of the cyclopropane

Stage B: 4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] benzoic acid (cis isomer)

By operating in an analogous manner starting with the cis isomer of tert-butyl 4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] benzoate, the desired product is obtained with a yield of 80%.

Melting point: 204° C.

EXAMPLE 4 4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] N-ethyl N-(2-methyl phenyl) benzenamide (cis isomer)

By operating as in Example 1, starting with the acid prepared according to Preparation 4 and commercial N-ethyl ortho-toluidine, the desired product is obtained.

Melting point: 133° C.

NMR of the proton in CDCl₃ at 250 MHz (in ppm) 1.20-1.23-1.26: N--CH₂ --CH₃ ; 1.68 to 1.86: CH₂ in position 3 of the cyclopropyl; 2.18 (s): CH₃ of the φ-CH₃ ; 2.30-2.32-2.34: CH in position 2 of the cyclopropyl; 3.62 to 3.69 and 4.10 to 4.20: N--CH₂ --CH₃ ;7.01 to 7.51: aromatic 12H's.

MS: MH⁺ =408⁺

EXAMPLE 5 4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] N-isobutyl benzenamide (cis isomer)

By operating as in Example 1, starting with the acid prepared according to Preparation 4 and commercial N-isobutyl amine, the desired product is obtained.

Melting point: 1400 C.

NMR of the proton in CDCl₃ at 250 MHz (in ppm) 0.99 (d): CH₃ of the isobutyl; 1.70 to 1.98 (m): CH₂ in position 3 of the cyclopropyl and CH of the isobutyl; 2.47 (m): CH in position 2 of the cyclopropyl (trans/F); 3.30 (m): CH₂ of the isobutyl; 6.20 (wt): NH; 7.20 to 7.35: aromatic 6H's; 7.80 (wd): aromatic 2H's.

EXAMPLE 6 4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] N-(2-methyl phenyl) benzenamide (cis isomer)

By operating as in Example 1, starting with the acid prepared according to Preparation 4 and commercial ortho-toluidine, the desired product is obtained.

Melting point: 172° C.

TLC: R_(f) =0.14 (eluant: hexane-ethyl acetate (8-2)).

Microanalysis for C₂₃ H₁₉ ClFNO=379.866

    ______________________________________                                                C %     H %    F %       Cl % N %                                       ______________________________________                                         Calculated                                                                              72.73     5.04   5.0     9.3  3.69                                      Found 72.5 4.9 4.8 9.5 3.6                                                   ______________________________________                                    

NMR of the proton in CDCl₃ at 250 MHz (in ppm) 1.803 to 2.025 (2H): CH₂ in position 3 of the cyclopropyl; 2.35 (s) and 2.45 0 2.57 (m) (4H): φ-CH₃ and CH in position 2 of the cyclopropyl (trans/F); 7.13 to 7.98 (13H): aromatic H's and NH

IR in CHCl₃ in cm⁻¹ 3444: ═C--NH; 1677: O═C<; 1615, 1589, 1570, 1526, 1510 and 1496: φ+secondary amide.

Preparation 7: 4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] benzoic acid (cis isomer)

Stage A: tert-butyl 4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] benzoate (cis isomers)

By operating as in Stage E of Preparation 1, using commercial 3,4-bromo styrene, the desired product is obtained.

NMR of the proton

1.60 (s): CO₂ tBu 7.28 to 8.03: aromatic 7H's

Stage B: 4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] benzoic acid (cis isomer)

By operating in the same manner as in Stage F of Preparation 1, the desired acid is obtained.

EXAMPLE 7 4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] N-(2-methyl phenyl) benzenamide (cis isomer) and its optically-active isomers.

By operating as in Example 1, starting with the acid prepared according to Preparation 7 and commercial ortho-toluidine, the desired product is obtained.

Melting point: 158° C.

NMR of the proton in CDCl₃ at 250 MHz (in ppm) 1.77 to 2.10: CH₂ in position 3 of the cyclopropyl; 2.35 (s): CH₃ of the φ-CH₃ ; 2.46 (d,d,d): CH in position 2 of the cyclopropyl (trans/F); 7.63 (s): NH; 7.12 to 7.92: aromatic 11H's.

Separation of optically-active isomers.

2 g of the product obtained in Example 7 is injected in batches of 500 mg over 260 g of CHIRALPAK AD® phase, 20μ with the heptane-ethanol-methanol 50-30-20 eluant mixture and at a flow rate of 100 ml/min. After distillation of the good fractions, dextrogyrated enantiomer A 830 mg (purity 99%) and levograted enantiomer B 850 mg (purity 96.6%) are collected. Enantiomer B is reinjected in batches of 425 mg under the same conditions in order to obtain 780 mg (purity 99.4%)

Controls:

The purities are determined by analytical HPLC on a chiralpak AD® column 25 cm×0.46 cm at a flow rate of 1 ml/min with the same eluant mixture. The detection takes place at 254 nm and the capacity factors are 1.44 and 2.35 respectively for the dextrogyrated and levogyrated enantiomers.

Enantiomer A: alphaD (0.6% in CHCl₃)=+261°.

Enantiomer B: alphaD (0.6% in CHCl₃)=-257°.

EXAMPLE 8 4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] N-isobutyl benzenamide (cis isomer)

By operating as in Example 1, starting with the acid prepared according to Preparation 7 and commercial N-isobutyl amine, the desired product is obtained.

Melting point: 132° C.

NMR of the proton in CDCl₃ at 250 MHz (in ppm) 0.97 (d), 1.00 (d): CH₃ of the isobutyl; 1.63 to 1.98 (3H): CH₂ in position 3 of the cyclopropyl and CH of the isobutyl; 2.45 (1H): CH in position 2 of the cyclopropyl (trans/F); 3.25 (t) (2H): CH₂ of the isobutyl; 6.05 (f): NH; 7.06 to 7.82 (7H): aromatic H's.

Starting with the trans isomers of the acids prepared according to Preparations 1 to 7, the following compounds are obtained:

EXAMPLE 9 4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] N-isobutyl benzenamide (trans isomer)

Melting point: 157° C.

NMR of the proton in CDCl₃ at 250 MHz (in ppm) 0.96 (d): CH₃ of the isobutyl; 1.65 to 2.08 (m): CH₂ in position 3 of the cyclopropyl and CH of the isobutyl; 2.99 (d,d,d J=8.5, 11.5 and 20): CH in position 2 of the cyclopropyl (cis/F); 3.24 (t): CH₂ of the isobutyl; 6.13 (wt): NH; 6.88 (d) and 7.11 (d): H of the 4-chloro phenyl; 7.16 (d) and 7.61 (d): H of the para-phenylene.

EXAMPLE 10 4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] N-(2-methyl phenyl) benzenamide (trans isomer)

TLC: R_(f) =0.16 (eluant: hexane-ethyl acetate (8-2)).

IR in CHCl₃ in cm⁻¹ 3450: C--NH; 1676: O═C; 1615, 1589, 1572, 1526, 1510 and 1495: φ+secondary amide.

By implementing one of the methods set out on the preceding pages, the following products were prepared.

In the following tables:

the asterisk in front of the Example number indicates that the pure cis isomer has been isolated and the double asterisk indicates that the trans isomer has been isolated,

TfO represents the trifluoromethyl sulphonyloxy radical,

Z₂ represents the 2-(pyrrolydin-1-yl) phenyl radical,

THP signifies tetrahydropyranyloxy.

                                      TABLE A                                      __________________________________________________________________________       #STR6##                                                                         -                                                                           Ex N.sup.o :                                                                       a b  c   d e v f      g  h    i  j R.sup.2                                 __________________________________________________________________________     2   H H  H   H H F Me     H  H    H  H H                                         4* H H Cl H H F Me H H H H Et                                                  6* H H Cl H H F Me H H H H H                                                   7* H Br Br H H F Me H H H H H                                                  7A H Br Br H H F Me H H H H H                                                  7B H Br Br H H F Me H H H H H                                                  10** H H Cl H H F Me H H H H H                                                 12* H Cl Cl H H F Me H H H H H                                                 13* H Cl Cl H H F Me H H H H Et                                                14** H Cl Cl H H H Me H H H H H                                                15* H Br Br H H F Me H H H H Et                                                16* H H MeO H H F Me H H H H Et                                                17* H Cl Cl Cl H F Me H H H H H                                                18* H CF.sub.3 Br H H F Me H H H H H                                           19* Cl H Cl H H F Me H H H H H                                                 20 Cl H Cl H H F Me H H H H H                                                  21** Cl H Cl H H F Me H H H H H                                                22* H H Br H H F Me H H H H H                                                  23* H Br H H H F Me H H H H H                                                  24* Cl H H H H F Me H H H H H                                                  25** Cl H H H H F Me H H H H H                                                 26* H PhO H H H F Me H H H H H                                                 27* H PhO H H H F Me H H H H Et                                                29* H H Me H H F Me H H H H H                                                  31* Cl H H H H F Me H H H H Et                                                 32* H CF.sub.3 Br H H F Me H H H H Et                                          33* H H CF.sub.3 H H F Me H H H H H                                            34 H H CF.sub.3 H H F Me H H H H H                                             35* Cl Cl H H H F Me H H H H H                                                 36* Cl Cl H H H F Me H H H H Et                                                37** H Br Br H H F Me H H H H Et                                               38* H H CF.sub.3 H H F Me H H H H Et                                           39** H H CF.sub.3 H H F Me H H H H Et                                          40* H TfO TfO H H F Me H H H H H                                               41** H Br Br H H F Me H H H H H                                                42** H H F H H F Me H H H H H                                                  43* H H F H H F Me H H H H H                                                   44* H Br Br H H F Me H H H H Pr                                                45* H Br Br H H F Me H H H H Me                                                46* Cl H H H Cl F Me H H H H H                                                 47* H Br Br H H F Me H H H H Bn                                                48* H Br Br H H F Me H H H H Bu                                                49* H H CF.sub.3 O H H F Me H H H H H                                          50* H H CHF.sub.2 O H H F Me H H H H H                                         51* H PhO F H H F Me H H H H H                                                 52* H H NO.sub.2 H H F Me H H H H H                                            53* H F F H H F Me H H H Me H                                                  56* H Br Br H H F H H tBu H H H                                                57* H Br Br H H F CH.sub.2 ═C(CH.sub.3) H H H H H                          58* H Br Br H H F MeS H H H H H                                                59* H Br Br H H F MeO H H H H H                                                60* H Br Br H H F H H cyclohexyl H H H                                         61* H Br Br H H F Ph H H H H H                                                 62* H Br Br H H F H Br H H H H                                                 63* H Br Br H H F Cl H H H H H                                                 64* H Br Br H H F H H H H H H                                                  65* H Br Br H H F Et H H H H H                                                 66* H Br Br H H F N57 C H H H H H                                              67* H Br Br H H F CF.sub.3 O H H H H H                                         68* H Br Br H H F PhO H H H H H                                                69* H Br Br H H F Br H H H H H                                                 70* H Br Br H H F H Cl MeO Cl H H                                              71* H Br Br H H F MeO H Cl Cl H H                                              72* H Br Br H H F H H F H H H                                                  73* H Br Br H H F H F H H H H                                                  74* H Br Br H H F H Cl Br Cl H H                                               75* H Br Br H H F NO.sub.2 H MeO H H H                                         76* H Br Br H H F H Cl Cl H H H                                                77* H Br Br H H F MeO H H Me H H                                               78* H Br Br H H F H MeO H MeO H H                                              80* H Br Br H H F H MeO MeO H H H                                              81* H Br Br H H F Me H H H Me Me                                               82* H Br Br H H F Me H MeO H H H                                               83* H Br Br H H F F H H H F H                                                  84* H Br Br H H F H H CO.sub.2 Me H H H                                        85* H Br Br H H F H H BnO H H H                                                86* H Br Br H H F CH3 H H H Me H                                               87* H Br Br H H F Cl H H H Cl H                                                88* H Br Br H H F MeO H H CF.sub.3 H H                                         89* H Br Br H H F Me Me H H H H                                                90* H Br Br H H F Me H Me H H H                                                91* H Br Br H H F H MeO H CF.sub.3 H H                                         92* H Br Br H H F Cl H H Me H H                                                93* H Br Br H H F H H MeO H H H                                                94 H Br Br H H F H H PhO H H W                                                 95* H Br Br H H F F H Me H H H                                                 96* H Br Br H H F H Cl Cl H H Me                                               97* H Br Br H H F MeO H H MeO H H                                              98* H Br Br H H F Me Cl H H H H                                                99* H Br Br H H F H PhO H H H H                                                100* H Br Br H H F MeO H H NO.sub.2 H H                                        101* H Br Br H H F H Br Br H H H                                               102* H Br Br H H F PhCO H H H H H                                              103* H Br Br H H F Cl H H Cl H H                                               104* H Br Br H H F H H NCCH.sub.2 H H H                                        105* H Br Br H H F Me H Me H Me H                                              106* H Br Br H H F Cl H Cl H H H                                               107* H Br Br H H F H Cl H Cl H H                                               108* H Br Br H H F H Me H Me H H                                               109* H Br Br H H F Me H H Cl H H                                               110* H Br Br H H F z.sub.2 H H H H H                                           111* H Br Br H H F CO.sub.2 Me H H Cl H H                                      112* H Br Br H H F tBu H H H H H                                               113** H Cl Cl H H H Me H H H H H                                               114** H Cl Cl H H H Me H H H H Et                                              115* H Cl Cl H H H Me H H H H H                                                116 H H Br H H H Me H H H H Et                                                 117** H Br Br H H H Me H H H H H                                               118 H Br Br H H H Me H H H Me H                                                119 H Cl cl H H H Cl H H H Cl H                                                120* H Cl Cl H H Br Me H H H H H                                               121* H Cl Cl H H Cl Me H H H H H                                               268 H Br Br H H F CHF.sub.2 O H H H H H                                        269 H F F H H F Me H H H H H                                                   270 H Br TfO Br H F Me H H H H H                                               271 H Br TfO H H F Me H H H H H                                                272 H Br TfO H H F Me H H H Me H                                               274 H Br CHF.sub.2 O Br H F Me H H H Me H                                      275 H Br CHF.sub.2 O Br H F Me H H H H H                                       276 H Br Br H H F Cl H Me H H H                                                282 H Br Br H H F OH H H H H H                                                 283 H Cl Cl H H F CH.sub.2 OH H H H H H                                        284 H Cl Cl H H F CH.sub.2 F H H H H H                                         285 H Cl Cl H H F CHO H H H H H                                                286 H Cl Cl H H F Me H H H Me H                                                287 H Cl Cl H H F Me H Me H H H                                                288 H Cl Cl H H F F H H H H H                                                  289 H Cl Cl H H F Cl H Me H H H                                                290 H Cl Cl H H F CN H H H H H                                                 291 H Cl Cl H H F OMe H H CF.sub.3 H H                                         292 H Br Br H H F Me H H H H Et                                                308 H Cl Cl H H F H H PhO H H H                                                317 H Br Br H H H Me H Me H H H                                                318 H Br Br H H H F H H H H H                                                  319 H Br Br H H H Cl H Me H H H                                                320 H Br Br H H H H H PhO H H H                                                321 H Br Br H H H H H CN H H H                                                 322 H Br Br H H H OMe H H CF.sub.3 H H                                         323 H Br Br H H H CH.sub.2 OH H H H H H                                        324 H Br Br H H H CH.sub.2 F H H H H H                                         30* H H MeO H H F Me H H H H H                                                 54* H Br Br H F F H H H H H H                                                  55* H Br Br H H F H H Me H H H                                                 79* H Br Br H H F MeOC(O) H H H H H                                            273 H Br CHF.sub.2 O H H F Me H H H H H                                        344 H H TfO H H F Me H H H H H                                                 345 H Cl H Cl H F Me H H H H H                                                 346 H Br Br H H F H Me H H H H                                               __________________________________________________________________________

                                      TABLE B                                      __________________________________________________________________________       #STR7##                                                                         -                                                                           Ex N.sup.o :                                                                       a b  c   d e v R.sub.1         R.sub.2                                     __________________________________________________________________________     1   H H  H   H H F (CH.sub.3).sub.2 CHCH.sub.2                                                                    H                                             3** H H Cl H H H (CH.sub.3).sub.2 CHCH.sub.2 H                                 5* H H Cl H H F (CH.sub.3).sub.2 CHCH.sub.2 H                                  8* H Br Br H H F (CH.sub.3).sub.2 CHCH.sub.2 H                                 9** H H Cl H H F (CH.sub.3).sub.2 CHCH.sub.2 H                                 122** H H F H H F (CH.sub.3).sub.2 CHCH.sub.2 H                                123* H H F H H F (CH.sub.3).sub.2 CHCH.sub.2 H                                 124* Cl H H H Cl F (CH.sub.3).sub.2 CHCH.sub.2 H                               125 Cl Cl H H H F (CH.sub.3).sub.2 CHCH.sub.2 H                                126 H F F H H F (CH.sub.3).sub.2 CHCH.sub.2 H                                  127* H H CHF.sub.2 O H H F (CH.sub.3).sub.2 CHCH.sub.2 H                       128* H H CF.sub.3 O H H F (CH.sub.3).sub.2 CCH.sub.2 H                         129* H Br Br H H F (CH.sub.3).sub.2 CHCH(CH.sub.3) CH.sub.3 CH.sub.2                                             130 H Br Br H H F CH.sub.3 (CH.sub.2).                                        sub.2 H                                       131 H Br Br H H F (CH.sub.3).sub.3 CH.sub.2 C(CH.sub.3).sub.2 H                                                  132 H Br Br H H F CH.sub.3 CH.sub.2                                           CH.sub.3 CH.sub.2                             133 H Br Br H H F CH.sub.3 (CH.sub.2).sub.3 H                                  134 H Br Br H H F (CH.sub.3).sub.2 CHCH(CH.sub.3) H                            135* H Br Br H H F (CH.sub.3).sub.2 CHCH.sub.2 CH(CH.sub.3) H                  136* H Br Br H H F (CH.sub.3).sub.2 CHCH.sub.2 CH.sub.2 H                      137* H Br Br H H F CH.sub.3 (CH.sub.2).sub.2 CH.sub.3                          138* H Br Br H H F CH.sub.3 (CH.sub.2).sub.5 H                                 139* H Br Br H H F (CH.sub.3).sub.3 CCH(CH.sub.3) H                            140 H Br Br H H F (CH.sub.3).sub.3 C H                                         141* H Br Br H H F (CH.sub.3).sub.3 CCH.sub.2 H                                142* H Br Br H H F CH.sub.3 CH.sub.2 CH(CH.sub.3) H                            143* H Br Br H H F CH.sub.3 CH.sub.2 CH(CH.sub.3)CH.sub.2 H                    144* H Br Br H H F CH.sub.3 CH.sub.3                                           145* H Br Br H H F (CH.sub.3).sub.2 CH H                                       146* H Br Br H H F CH.sub.3 CH.sub.2 H                                         147* H Br Br H H F CH.sub.3 CH.sub.2 CH(C.sub.2 H.sub.5) H                     148* H Br Br H H F (C.sub.2 H.sub.5)CH(CH.sub.3)CH.sub.2 CH(CH.sub.3) H        149* H Br Br H H F (CH.sub.3).sub.2 CH(CH.sub.2).sub.3 CH(CH.sub.3) H                                            150* H Br Br H H F (CH.sub.3).sub.3                                           C(CH.sub.2).sub.2 H                           151* H Br Br H H F (CH.sub.3).sub.2 CHCH.sub.2 CH.sub.3                        152* H Br Br H H F (CH.sub.3).sub.3 C CH.sub.3                                 153* H Br Br H H F CH.sub.3 CH.sub.2 C(CH.sub.3).sub.2 H                       154 H Br Br H H F CH.sub.3 (CH.sub.2).sub.2 CH(CH.sub.3) H                     155 H Br Br H H F (CH.sub.3).sub.2 CH (CH.sub.3).sub.2 CH                      156 H Br Br H H F (CH.sub.3).sub.2 CH Et                                       157* H H Br H H H (CH.sub.3).sub.2 CHCH.sub.2 H                                158* H Br Br H H H (CH.sub.3).sub.2 CHCH.sub.2 H                               159 H Cl Cl H H H (CH.sub.3).sub.2 CHCH(CH.sub.3) H                            160** H Cl Cl H H F (CH.sub.3).sub.2 CHCH.sub.2 H                              161* H Cl Cl H H Cl (CH.sub.3).sub.2 CHCH.sub.2 H                              162 H Cl Cl H H Cl (CH.sub.3).sub.2 CHCH(CH.sub.3) H                           163* H Cl Cl H H Br (CH.sub.3).sub.2 CHCH.sub.2 H                              164* H Br Br H H F CH.sub.2 ═C(CH.sub.3)CH.sub.2 H                         165* H Br Br H H F CH.sub.2 ═CHCH.sub.2 H                                  166* H Br Br H H F CH.tbd.CCH.sub.2 H                                          167* H Br Br H H F CH.sub.2 ═C(Cl)CH.sub.2 H                               168* H PhO F H H F (CH.sub.3).sub.2 CHCH.sub.2 H                               169* H F F H H F C.sub.6 H.sub.5 --CH(CH.sub.3)(R) H                           170* H Br Br H H F (2-Me C.sub.6 H.sub.4)CH.sub.2 H                            171* H Br Br H H F (4-Cl C.sub.6 H.sub.4)CH.sub.2 H                            172* H Br Br H H F (C.sub.6 H.sub.5)CH.sub.2 H                                 173 H Br Br H H F C.sub.6 H.sub.5 --CH(CH.sub.3) H                             174* H Br Br H H F cyclobutyl H                                                175* H Br Br H H F cyclohexyl H                                                176* H Br Br H H F cyclopentyl H                                               177* H Br Br H H F cyclopropyl H                                               178* H Br Br H H F (cyclopropyl) methyl H                                      179* H Br Br H H F C.sub.6 H.sub.5 --CH.sub.2 (CH.sub.2).sub.3 H                                                 180 H Br Br H H F (3-CF.sub.3 C.sub.6                                         H.sub.4)CH.sub.2 C(CH.sub.3) H                                                  181* H Br Br H H F (cyclohexyl)                                               methyl H                                      182 H Br Br H H F adamantyl H                                                  183* H Br Br H H F 2-methyl cyclohexyl H                                       184* H Br Br H H F CH.tbd.CC(CH.sub.3).sub.2 H                                 185* H Br Br H H F 2,3-dihydro 1-indenyl H                                     186* H Br Br H H F 1-naphthyl H18                                              187* H Br Br H H F N.tbd.CCH.sub.2 H                                           188 H Br Br H H F (2-thienyl) methyl H                                         190* H Br Br H H F 4(R)-tBu cyclohexyl HH                                      192* H Br Br H H F tBuOC(═O)CH.sub.2 H                                     193* H Br Br H H F MeSCH.sub.2 CH.sub.2 H                                      194* H Br Br H H F ClCH.sub.2 (CH.sub.2).sub.2 H                               195 H Br Br H H F 2-(1,4-oxazin-1-yl) ethyl H                                  196* H Br Br H H F CF.sub.3 CH.sub.2 H                                         197* H Br Br H H F (C.sub.7 F.sub.15)CH.sub.2 H                                198* H Br Br H H F (oxolann-2-yl) methyl H                                     199* H Br Br H H F 4-Me thiazol-2-yl H                                         200* H Br Br H H F (C.sub.6 H.sub.5).sub.2 CH H                                201* H Br Br H H F (C.sub.6 H.sub.5)CH.sub.2 CH(C.sub.6 H.sub.5) H                                               202* H Br Br H H F (C.sub.6 H.sub.5).s                                        ub.2 CHCH.sub.2 H                             203* H Br Br H H F (MeO).sub.2 CHCH.sub.2 H                                    204* H Br Br H H F MeOCH.sub.2 CH.sub.2 H                                      205* H Br Br H H F 3-(2-oxo pyrrolidino) propyl H                              206* H Br Br H H F CH.sub.2 ═C(Br)CH.sub.2 H                               207* H Br Br H H F FCH.sub.2 CH.sub.2 H                                        208* H Br Br H H F [MeOC(═O)](C.sub.6 H.sub.5)CH H                         209* H Br Br H H F (1-Et pyrrolidin-2yl) methyl H                              210* H Br Br H H F 5-Me isoxazol-3-yl H                                        211* H Br Br H H F CH.sub.2 (OH)CH(CH.sub.3) H                                 212 H Cl Cl H H H cyclobutyl H                                                 213 H Br Br H H F (4-Me thiazol-5-yl) methyl Me                                214 Br Br H H F  (CH.sub.3).sub.2 NCH.sub.2 CH.sub.2 CH.sub.3                  215* H Br Br H H F (CH.sub.3).sub.2 NCH.sub.2 CH(CH.sub.3) H                   216* H Br Br H H F (CH.sub.3).sub.2 NCH.sub.2 CH.sub.2 H                       217* H Br Br H H F (CH.sub.3).sub.2 CH (CH.sub.3).sub.2 CH                     218* H Br Br H H F (CH.sub.3).sub.2 CH CH.sub.3 CH.sub.2                       219* H Br Br H H F N(R.sub.1)(R.sub.2): 1,4-thiazin-4-yl                       220* H Br Br H H F N(R.sub.1)(R.sub.2): aziridin-1-yl                          221 H Br Br H H F N(R.sub.1)(R.sub.2): piperidin-1-yl                          222 H Br Br H H F N(R.sub.1)(R.sub.2): pyrrolidin-1-yl                         223 H Br Br H H F N(R.sub.1)(R.sub.2): 1,4-oxazin-4-yl                         224 H Br Br H H F N(R.sub.1)(R.sub.2): 2-Me piperidin-1-yl                     225 H Br Br H H F pyrrolidin-1-yl H                                            226* H Br Br H H F 1,4-oxazin-4-yl H                                           227 H Br Br H H F (3,5-diCl C.sub.6 H.sub.3)NH H                               228* H Br Br H H F piperidin-1-yl H                                            229* H Br Br H H F (CH.sub.3).sub.2 N H                                        277 H Br Br H H F (1,5-diMe)piperidinyl-1-yl H                                 278 H Br TfO Br H F CH.sub.3 CH(CH.sub.3)CH.sub.2 H                            279 H Br CHF.sub.2 O Br H F CH.sub.3 CH(CH.sub.3)CH.sub.2 H                    280 H Br Br H H F pyridin-3-yl H                                               281 H Br Br H H F N(R.sub.1)(R.sub.2): 2-CH.sub.2 OH pyrrolidin-1-yl                                             293 H Br Br H H F 2-Cl 3-pyridinyl H                                           294 H Cl Cl H H F benzazetidine H                                              295 H Cl Cl H H F (CH.sub.3).sub.3                                            CCH.sub.2 C(CH.sub.3).sub.2 H                 296 H Cl Cl H H F C.sub.6 H.sub.5 --CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2                                         H                                             297 H Cl Cl H H F N(R.sub.1)(R.sub.2): 1,4-oxazin-4-yl                         298 H Cl Cl H H F (CH.sub.3).sub.2 CHCH.sub.2 H                                299 H Cl Cl H H F (CH.sub.3).sub.2 CHCH(CH.sub.3) H                            300 H Cl Cl H H F cyclopentyl H                                                301 H Cl Cl H H F 1,4-oxazin-4-yl H                                            302 H Cl Cl H H F H H                                                          303 H Cl Cl H H F (CH.sub.3).sub.2 C═CHCH.sub.2 H                          304 H Cl Cl H H F CH.sub.3 ═C(CH.sub.3)CH.sub.2 H                          305 H Cl Cl H H F Cl--CH.sub.3 CH.sub.3 CH.sub.2 H                             306 H Cl Cl H H F (CH.sub.3).sub.2 CHCH.sub.3 CH.sub.2 H                       307 H Cl Cl H H F CH.sub.3 H                                                   309 H Cl Cl H H F CH.sub.2 ═C(Br)CH.sub.2 H                                310 H Cl Cl H H F CH.sub.3 --S--CH.sub.3 CH.sub.2 H                            311 H Cl Cl H H F C.tbd.CCH.sub.2 H                                            312 H Cl Cl H H F C.sub.6 H.sub.5 --CH(CH.sub.3) H                             313 H Cl Cl H H F (CH.sub.3).sub.2 NCH.sub.2 CH.sub.2 CH.sub.3                 314 H Cl Cl H H F 2-THP H                                                      315 H CL Cl H H F cyclohex-3-en-1-yl H                                         316 H Cl Cl H H F tetrazole H                                                  325 H Br Br H H H (CH.sub.3).sub.3 CCH.sub.2 C(CH.sub.3).sub.2 H                                                 326 H Br Br H H H C.sub.6 H.sub.5                                             --CH.sub.2 CH.sub.2 CH.sub.2 CH.sub. H        327 H Br Br H H H N(R.sub.1)(R.sub.2): 1,4-oxazin-4-yl                         328 H Br Br H H H (CH.sub.3).sub.2 CHCH.sub.2 H                                329 H Br Br H H H (CH.sub.3).sub.2 CHCH(CH.sub.3) H                            330 H Br Br H H H cyclopentyl H                                                331 H Br Br H H H 1,4-oxazin-4-yl H                                            332 H Br Br H H H CH.sub.2 ═C(CH.sub.3)CH.sub.2 H                          333 H Br Br H H H (CH.sub.3).sub.2 CHCH.sub.2 CH.sub.2 H                       334 H Br Br H H H CH.sub.3 H                                                   335 H Br Br H H H CH.sub.2 ═C(Br)CH.sub.2 H                                336 H Br Br H H H CH.sub.3 SCH.sub.2 CH.sub.2 H                                337 H Br Br H H H CH.tbd.CCH.sub.2 H                                           338 H Br Br H H H C.sub.6 H.sub.5 --CH(CH.sub.3) H                             339 H Br Br H H H (CH.sub.3).sub.2 NCH.sub.2 CH.sub.2 CH.sub.3                 340 H H TfO H H F cyclobutyle H                                                341 H H TfO H H F (CH.sub.3).sub.2 CHCH(CH.sub.3) H                          __________________________________________________________________________

                  TABLE C                                                          ______________________________________                                           #STR8##                                                                        Ex N.sup.o :                                                                            Q             V    R.sub.1    R.sub.2                               ______________________________________                                         230**  5-bromo 2-naphthyl                                                                           F      2-methyl phenyl                                                                           ethyl                                     231* 5-bromo 2-naphthyl F 2-methyl phenyl ethyl                                232* 5-bromo 2-naphthyl F 2-methyl phenyl H                                    233** 5-bromo 2-naphthyl F 2-methyl phenyl H                                   234* 2-naphthyl F 2-methyl phenyl H                                            235* 2-naphthyl F 2-methyl propyl H                                            236* 6-bromo 1-naphthyl F 2-methyl phenyl H                                    237 6-bromo 1-naphthyl F 2-methyl propyl H                                     238 6-bromo 1-naphthyl F 1,2-dimethyl propyl H                                 239 7-bromo 1-naphthyl F 2-methyl propyl H                                   ______________________________________                                    

                  TABLE D                                                          ______________________________________                                           #STR9##                                                                         - (In the following table the phenylene radicals are bonded to               the amide function by the carbon in position 1 and the                         naphtylene radicals by the carbons in positions 1 or 2)                         Ex N.sup.o :                                                                           Q.sub.2        v    R.sub.1   R.sub.2                                ______________________________________                                         240*  1,3-phenylene  F      2-methyl phenyl                                                                          H                                          240** 1,3-phenylene F 2-methyl phenyl H                                        241** 1,3-phenylene F 2-methyl phenyl CH.sub.3 CH.sub.2                        242* 1,3-phenylene F 2-methyl phenyl CH.sub.3 CH.sub.2                         243* 1,3-phenylene F 2-methyl propyl H                                         244* 2-methyl 1,4-phenylene F 2-methyl phenyl H                                245* 2-methyl 1,4-phenylene F 2-methyl propyl H                                246 2-methyl 1,4-phenylene CH.sub.3 2-methyl phenyl H                          247** 2,3,5,6-tetrafluoro F 2-methyl phenyl H                                   1,4-phenylene                                                                 248* 3-methyl 1,4-phenylene F 2-methyl phenyl H                                249* 2-methyl 1,4-phenylene F 2-methyl propyl H                                250* 2-chloro 1,4-phenylene F 2-methyl phenyl H                                251* 2,5-naphthylene F 2-methyl phenyl H                                       252* 2,5-naphthylene F 2-methyl propyl H                                       253* 1,5-naphthylene F 2-methyl phenyl H                                       254* 1,5-naphthylene F 2-methyl propyl H                                       255* 2-acetylamino 5-chloro F 2-methyl phenyl H                                 1,4-phenylene                                                                 256* 2-amino 5-chloro F 2-methyl phenyl H                                       1,4-phenylene                                                                 257** 2,3,5,6-tetrafluoro H 2-methyl phenyl CH.sub.3 CH.sub.2                   1,4-phenylene                                                                 258** 2-chloro 1,4-phenylene H 2-methyl phenyl H                               259** 2-chloro 1,4-phenylene H 2-methyl propyl H                               260* 3-fluoro 1,4-phenylene H 2-methyl phenyl H                                261* 3-fluoro 1,4-phenylene H 2-methyl propyl H                                342 1,4-naphtylene H 2-methyl phenyl H                                         343 5-Cl 2(1-methyl- F 2-methyl phenyl H                                        ethylidene)amino                                                               1,4-phenylene                                                               ______________________________________                                    

                  TABLE E                                                          ______________________________________                                           #STR10##                                                                        - (In the following table, the position 1 of Q.sub.1 is bonded to            the anilide group)                                                              Ex N.sup.o :                                                                           b      c    Q.sub.1     R.sub.1   R.sub.2                            ______________________________________                                         262   Br     Br     3,3-dibromo 2-methyl phenyl                                                                          H                                         1,2-cyclopropanediyl                                                        263 H Cl 1,2-difluoro 2-methyl phenyl H                                           1,2-cyclopropanediyl                                                      ______________________________________                                    

                  TABLE F                                                          ______________________________________                                           #STR11##                                                                       Ex N.sup.o :                                                                              o       c    v    R.sub.1     R.sub.2                             ______________________________________                                         264      Br      Br     F    2-methyl phenyl                                                                            H                                       265 Br Br F 1,2-dimethyl propyl                                                345 Br Br F 2-methyl phenyl H                                                ______________________________________                                    

In the table below, the physical analysis results of products of formula (I) are given.

    ______________________________________                                         Products of                                                                      examples M.p. ° C. Rf                                                 ______________________________________                                         4           133° C.                                                                            0.19 (hexane/AcOEt 7/3)                                   6 172° C. 0.14 (hexane/AcOEt 8/2)                                       7 158° C. 0.2 (hexane/AcOEt 7/3)                                        12 148° C. 0.2 (hexane/AcOEt 7/3)                                       13 126.8° C. 0.18 (hexane/AcOEt 7/3)                                    15 130.1° C. 0.07 (ether isopropylique/                                   heptane/1/1)                                                                 17 195° C. 0.25 (hepatne/AcOEt 7/3)                                     20 -- 0.1 (heptane/AcOEt 85/15)                                                23 128° C. 0.16 (heptane/AcOEt 7/3)                                     32 -- 0.12 (heptane/AcOEt 7/3)                                                 33 -- 0.25 (heptane/AcOEt 7/3)                                                 38 -- 0.13 (heptane/AcOEt 7/3)                                                 45 147° C. 0.18 (hexane/AcOEt 7/3)                                      47 107.8° C. 0.18 (hexane/AcOEt 8/2)                                    49 137° C. --                                                           50 124° C. 0.45 (heptane/AcOEt 7/3)                                     54 138.1° C. 0.25 (heptane/AcOEt 7/3)                                   72 -- 0.22 (heptane/AcOEt 7/3)                                                 73 -- 0.25 (heptane/AcOEt 7/3)                                                 82 -- 0.08 (heptane/AcOEt 7/3)                                                 86 -- 0.24 (hexane/AcOEt 7/3)                                                  105 -- 0.48 (hexane/AcOEt 7/3)                                                 113 156.6° C. 0.3 (heptane/AcOEt 1/1)                                   114 122.3° C. 0.25 (heptane/AcOEt 1/1)                                  117 163.6° C. 0.32 (heptane/AcOEt 1/1)                                  121 141° C. 0.1 (heptane/AcOEt 8/2)                                     284 164° C. 0.15 (heptane/Etheriso 1/1)                                 292 -- 0.5 (heptane/AcOEt 1/1)                                                 8 132° C. 0.17 (hexane/AcOEt 7/3)                                       128 139° C. 0.14 (hexane/AcOEt 7/3)                                     167 136° C. 0.15 (hexane/AcOEt 7/3)                                     174 189.9° C. 0.23 (heptane/AcOEt 1/1)                                  194 -- 0.2 (CH.sub.2 Cl.sub.2)                                                 226 -- 0.02 (heptane/AcOEt 7/3)                                                293 -- 0.25 (CH.sub.2 Cl.sub.2 /TEA 99/1)                                      231 -- 0.2 (heptane/AcOEt 7/3)                                                 232 -- 0.25 (heptane/AcOEt 7/3)                                                236 184° C. 0.32 (heptane/dioxane 6/4)                                  244 159° C. 0.24 (heptane/AcOEt 7/3)                                    264 -- 0.42 (heptane/AcOEt 1/1)                                                265 -- 0.28 (hexane/AcOEt 7/3)                                               ______________________________________                                    

Preparations of compositions.

In the examples of compositions hereafter, the following signs mean:

* Surfactant.

# Reacts by forming the polyurea walls of the micro-capsules.

    ______________________________________                                         1. Emulsifiable concentrate.                                                     Active ingredient 10.00                                                        Ethoxylated alkylphenol * 7.50                                                 Alklarylsulphonate * 2.50                                                      C8-13 aromatic solvent 80.00                                                    100.00                                                                        2. Emulsifiable concentrate.                                                   Active ingredient 10.00                                                        Ethoxylated alkylphenol * 2.50                                                 Alkylarylsulphonate * 2.50                                                     Ketonic solvent 64.00                                                          C8-13 aromatic solvent 18.00                                                   Antioxidant 3.00                                                                100.00                                                                        3. Wettable powder.                                                            Active ingredient 5.00                                                         C8-13 aromatic solvent 7.00                                                    C18 aromatic solvent 28.00                                                     Kaolin 10.00                                                                   Alkylarylsulphonate * 1.00                                                     Naphthalenesulphonic acid * 3.00                                               Diatomaceous earth 46.00                                                        100.00                                                                        4. Dusting powder.                                                             Active ingredient 0.50                                                         Talc 99.50                                                                      100.00                                                                        5. Bait.                                                                       Active ingredient 0.5                                                          Sugar 79.5                                                                     Paraffin wax 20.0                                                               100.00                                                                        6. Concentrate in emulsion.                                                    Active ingredient 5.00                                                         C8-13 aromatic solvent 32.00                                                   Cetyl alcohol 3.00                                                             Polyoxyethyleneglycerol monooleate * 0.75                                      Polyoxyethylenesorbitan esters * 0.25                                          Silicon solution 0.1                                                           Water 58.9                                                                      100.00                                                                        7. Concentrate in suspension.                                                  Active ingredient 10.00                                                        Ethoxylated alkylphenol * 3.00                                                 Silicon solution 0.1                                                           Alkanediol 5.0                                                                 Fumed silica 0.50                                                              Xanthan gum 0.20                                                               Water 80.0                                                                     Buffer 1.2                                                                      100.00                                                                        8. Microemulsion.                                                              Active ingredient 10.00                                                        Polyoxyethyleneglycerol monooleate * 10.00                                     Alkanediol 4.00                                                                Water 76.00                                                                     100.00                                                                        9. Granules dispersible in water.                                              Active ingredient 70.00                                                        Polyvinylpyrrolidine 2.50                                                      Ethoxylated alkylphenol 1.25                                                   Alkylarylsulphonate 1.25                                                       Kaolin 25.00                                                                    100.00                                                                        10. Granules.                                                                  Active ingredient 2.00                                                         Ethoxylated alkylphenol * 5.00                                                 Alkylarylsulphonate * 3.00                                                     C8-13 aromatic solvent 20.00                                                   Kieselguhr granules 70.00                                                       100.00                                                                        11. Aerosol (spray).                                                           Active ingredient 0.3                                                          Piperonyibutoxide 1.5                                                          C8-13 saturated hydrocarbon solvent 58.2                                       Butane 40.0                                                                     100.00                                                                        12. Aerosol (spray).                                                           Active ingredient 0.3                                                          C8-13 saturated hydrocarbon solvent 10.0                                       Sorbitan monooleate * 1.0                                                      Water 40.0                                                                     Butane 48.7                                                                     100.00                                                                        13. Aerosol (spray).                                                           Active ingredient 1.00                                                         CO.sub.2 3.00                                                                  Polyoxyethyleneglycerol monooleate * 1.40                                      Propanone 38.00                                                                Water 56.60                                                                     100.00                                                                        14. Varnishes.                                                                 Active ingredient 2.50                                                         Resin 5.00                                                                     Antioxidant 0.50                                                               Very aromatic white spirit 92.0                                                 100.00                                                                        15. Spray (ready-to-use).                                                      Active ingredient 0.10                                                         Antioxidant 0.10                                                               Odourless kerosene 99.8                                                         100.00                                                                        16. Potentialized spray (ready-to-use).                                        Active ingredient 0.10                                                         Piperonylbutoxide 0.50                                                         Antioxidant 0.10                                                               Odourless kerosene 99.30                                                        100.00                                                                        17. Microcapsules                                                              Active ingredient 10.0                                                         C8-13 aromatic solvent 10.0                                                    Aromatic diisocyanate # 4.5                                                    Ethoxylated alkylphenol * 6.0                                                  Alkyldiamine # 1.0                                                             Diethylenetriamine 1.0                                                         Concentrated hydrochloric acid 2.2                                             Xanthan gum 0.2                                                                Fumed silica 0.5                                                               Water 64.6                                                                      100.00                                                                        18. Dispersible concentrate.                                                   Active ingredient 5.0                                                          N-methylpyrrolidinone 15.00                                                    N-alkylpyrrolidinone 53.00                                                     C8-13 aromatic solvent 16.00                                                   Nonylphenol polyoxyethylenic ether                                             phosphate 6.00                                                                 Ethoxylated alkylphenol 3.50                                                   Alkylarylsulphonate 1.30                                                       Polyalkyleneglycol ether 0.20                                                   100.00                                                                        19. Soluble concentrate.                                                       A homogeneous mixture made of:                                                 Active ingredient 0.25                                                         Piperonyl butoxide 1.00                                                        Tween 80 0.25                                                                  Topanol A 0.1                                                                  Water 98.40                                                                    20. Emulsifiable concentrate.                                                  The following are intimately mixed:                                            Active ingredient 0.015                                                        Piperonyl butoxide 0.5                                                         Topanol A 0.1                                                                  Tween 80 3.5                                                                   Xylene 95.885                                                                ______________________________________                                    

BIOLOGICAL STUDY

A) Study on Phaedon cochleariae

The product is dissolved at the desired concentration in an acetone--water (50-50) mixture. Foliar discs of Chinese cabbage (Brassica pekinensis) are immersed for five seconds in the solution, then left to dry for one hour. Ten adults (a mixture of male and female) are put in a Petri dish each containing a foliar disc. The dishes are kept at a temperature of 25° C., with a photoperiod of twelve hours. After seven days, the mortality of the insects is checked, and the surface area of the leaves consumed is evaluated.

The following products have a good activity starting from a dose of 30 ppm: products of Examples 1, 4, 5, 6, 7, 8, 12, 13, 17, 18, 231, 232, 45, 128, 226, 86, 87, 141, 145, 194, 105, 284, 264, 292.

B) Study on Spodoptera littoralis

The product is dissolved at the desired concentration in an acetone-water (50-50) mixture. Bean leaves (Phaseolus vulgaris, Delinel var.) are immersed for five seconds in the solution, then left to dry in a Petri dish for one hour. Ten Spodoptera littoralis larvae are then put in each dish. The dishes are kept at a temperature of 25° C., with a photoperiod of twelve hours. After seven days, the mortality of the larvae is checked, and the surface area of the leaves consumed is evaluated.

The following products have a good activity starting from a dose of 30 ppm: products of Examples 4, 5, 6, 7, 8, 12, 13, 15, 17, 18, 20, 22, 23, 32, 33, 38, 44, 45, 47, 48, 49, 50, 128, 129, 344, 236, 345, 54, 174, 175, 178, 63, 346, 176, 65, 66, 134, 69, 72, 73, 226, 82, 83, 86, 87, 89, 90, 141, 142, 228, 143, 145, 293, 206, 105, 167, 284, 113, 114, 30117, 159, 212, 264, 292, 121, 265, 345.

C) Study on Heliothis virescens

The product is dissolved at the desired concentration in an acetone-water (50-50) mixture. 50 ul of solution is deposited on the surface of a small well containing about 2 grams of vegetable-based artificial medium. A neonate larva of Heliothis virescens is then put into each well, which is sealed with a sheet of cellophane. The tests are kept at a temperature of 25° C., with a photoperiod of twelve hours. The mortality of the larvae is checked after seven days.

The following products have a good activity starting from a dose of 30 ppm: products of Examples 4, 5, 6, 7, 12, 22, 32, 33, 38, 49, 50, 54, 175, 63, 65, 69, 72, 83, 86, 89, 90, 105, 284, 117, 244, 292, 345.

D) Study of the activity on Diabrotica

The test insects are final-stage larvae of Diabrotica undecimpunctata.

A disc of 9 cm diameter filter paper, placed at the bottom of a Petri dish, is treated using 1 cm³ of acetonic solution. After drying, 15 larvae per dose are deposited and the mortality check is carried out 24 hours after the treatment.

The following products have a good activity starting from a dose of 30 ppm: products of Examples 134, 81, 86. 

We claim:
 1. A compound selected from the group consisting of all stereoisomeric forms and mixtures thereof of a compound of the formula ##STR12## wherein Q and Q₂ are individually selected from the group consisting of aryl and naphthyl unsubstituted or substituted by at least one member of the group consisting of halogen, methylenedioxy, difluoromethylenedioxy, tetrafluoroethylenedioxy, --CN, --NO₂, cyanato, thiocyanato, pentafluorothio and fluorosulfonyl, a and b are individually 0 or 1, X₁ and X₂ are --O-- or --S--, Q₁ is cyclopropanediyl unsubstituted or substituted with 1 to 2 halogens and R₁ and R₂ are individually selected from the group consisting of hydrogen, saturated or unsaturated hydrocarbon of up to 12 carbon atoms and aryl of up to 12 carbon atoms.
 2. A compound of claim 1 wherein Q is phenyl or naphthyl unsubstituted or substituted with 1 to 3 substituents of claim
 1. 3. A compound of claim 1 wherein Q-(CH₂)_(a) -(X₁)_(b) is in trans position to ##STR13##
 4. a compound of claim 1 wherein Q₁ is unsubstituted or substituted with 1 to 2 methyl(s) or 1 to 2 halogens.
 5. A compound of claim 1 wherein Q is selected from the group consisting of phenyl, 2-chloro phenyl, 3-chloro phenyl, 3-bromophenyl, 3-(trifluoromethyl) phenyl, 4-chloro phenyl, 4-bromo phenyl, 4-iodo phenyl, 4-(trifluoromethyl) phenyl, 4-nitrophenyl, 4-methoxy phenyl, 4-(difluoromethoxy) phenyl, 4-(trifluoro-methoxy) phenyl, 3-bromo 4-(difluoromethoxy) phenyl, 4-(2,2-dibromo ethenyl) phenyl, 4-ethynyl phenyl, 4-benzyl phenyl, 3,4-dibromo phenyl, 2,4-dichlorophenyl, 3,4-dichloro phenyl, 3,4-difluorophenyl, 3-chloro 4-iodo phenyl, 4-bromo 3-chloro phenyl, 4-bromo 2-fluoro phenyl, 4-bromo 3-fluoro phenyl, 4-bromo 3-(trifluoromethyl) phenyl, 4-chloro 3-(trifluoro-methyl) phenyl, 3,5-bis(trifluoromethyl) phenyl, 3,4,5-trichloro phenyl, 4-bromo 3,5-dichloro phenyl, 3-phenoxyphenyl, 4-(fluoro 3-phenoxy) phenyl, 3-bromo 4-(trifluoromethylsulphonyloxy) phenyl, 3,4-bis(trifluoro-methylsulphonyloxy) phenyl, 2-naphthyl, 5-bromo 2-naphthyl and 6-bromo 1-napthyl.
 6. A compound of claim 1 wherein Q₁ is selected from the group consisting of 1,2-cyclopropanediyl, 1-fluoro 1,2-cyclopropanediyl, 1-chloro 1,2 -cyclopropanediyl, 1-bromo 1,2-cyclopropanediyl, 1-methyl 1,2-cyclopropanediyl, 3,3-dibromo 1,2-cyclopropanediyl and 1,2-difluoro 1,2-cyclopropanediyl.
 7. A compound of claim 1 wherein Q₂ is selected from the group consisting of ortho-phenylene, meta-phenylene, paraphenylene, 1,2-naphthylene, 1,3-naphthylene, 1,4-naphthylene, 1,5- naphthylene, 2,5-naphthylene, 4,5-indenylene, 4,6-indenylene, 4,7-indenylene, 4,5-indanylene, 4,6-indanylene, 4,7-indanylene, 1,2,3,4-tetrahydro 5,6-naphthylene, 1,2,3,4-tetrahydro 5,7-naphthylene, 1,2,3,4-tetrahydro 5,8-naphthylene, non substituted or substituted by 1 to 4 substituants.
 8. A compound of claim 1 wherein Q₂ is selected from the group consisting of 2-methyl-1,4-phenylene, 2,3,5,6-tetrafluoro 1,4-phenylene, 3-methyl 1,4-phenylene, 2-chloro 1,4-phenylene, 2-acetylamino 5-chloro 1,4-phenylene, 2-amino 5-chloro 1,4-phenylene, 2-dimethyl-amino 5-chloro 1,4-phenylene.
 9. A compound of claim 1 wherein R₂ is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms, benzyl, an ethoxymethyl, a propoxymethyl.
 10. A compound of claim 1 wherein selected from the group consisting of ka and b are
 0. -4-(1-fluoro 2-phenyl cyclopropyl) N-isobutyl benzenamide (cis+trans isomers, cis/trans=3/2)4-(1-fluoro 2-phenyl cyclopropyl) N-(2-methyl phenyl) -benzenamide (cis+trans isomers, cis/trans=3/1) 4-[2-(4-chloro phenyl) cyclopropyl] N-isobutyl benzenamide (trans isomer) 4-[2-(4chloro phenyl) 1-fluoro cyclopropyl] N-ethyl N-(2-methyl phenyl) benzenamide (cis isomer) 4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] -N-(2-methyl phenyl) benzenamide (cis isomer) 4-[2-(4chloro phenyl) 1-fluoro cyclopropyl] -N-isobutyl benzenamide (cis isomer) 4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] N-isobutyl benzenamide (cis isomer) 4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] -N-(2-methyl phenyl) benzenamide (cis isomer) 4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] N-isobutyl benzenamide (trans isomer) 4-[2-(4-chloro phenyl) 1-fluoro cyclopropyl] N-(2-methyl phenyl) benzenamide (trans isomer) 4-[2-(3,4-dichloro phenyl) 1-fluoro cyclopropyl] N-(2-methyl phenyl) benzenamide (cis isomer) 4-[2-dichloro phenyl) 1-fluoro cyclopropyl] N-ethyl N-(2-methyl phenyl) benzenamide (cis isomer) 4-[3,4,5-trichloro phenyl) 1-fluoro cyclopropyl] N-(2-methyl phenyl) benzenamide (cis isomer) 4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] N-methyl N-(2-methyl phenyl) benzenamide (cis isomer) 4-[2-(4-trifluoromethoxy phenyl) 1-fluoro cyclopropyl] N-(2-methyl phenyl) benzenamide (cis isomer) 4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] N-(2,6-dimethyl phenyl) benzenamide (cis isomer) 4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] N-(2,4,6-trimethyl phenyl) benzenamide (cis isomer) 4-[2-(3,4-dichloro phenyl) 1-dluoro cyclopropyl] N-benzenamide (cis isomer) 4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] N-(2-methyl phenyl) benzene thioamide (cis isomer) 4-[2-(3,4-dibromo phenyl) 1-fluoro cyclopropyl] N-ethyl N-(2-methyl phenyl) benzene thioamide (cis isomer) 4-[2-(3,4dibromo phenyl) 1-fluoro cyclopropyl] N-(1,4-oxazin-4-yl) benzenamide (cis isomer).
 11. A compound of claim 1 wherein a and b are
 0. 